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PubMed2000

Improved cerebral blood supply and oxygenation by aortic balloon occlusion combined with intra-aortic vasopressin administration during experimental cardiopulmonary resuscitation.

BACKGROUND: Intravenous administration of vasopressin during cardiopulmonary resuscitation (CPR) has been shown to improve myocardial and cerebral blood flow. Aortic balloon occlusion during CPR may also augment myocardial and cerebral blood flow and can be used as a central route for the administration of resuscitative drugs. We hypothesized that, as compared with intravenously administered vasopressin, the administration of this drug above the site of an aortic balloon occlusion would result in a greater increase in cerebral perfusion and oxygenation during CPR and after restoration of spontaneous circulation (ROSC). METHODS: Twenty piglets were subjected to 5 min of ventricular fibrillation followed by 8 min of closed-chest CPR and were treated with 0.4 U kg(-1) boluses of vasopressin intravenously (the IV-vasopressin group with sham aortic balloon) or above the site for an aortic balloon occlusion (the balloon-vasopressin group). The aortic balloon catheter was inflated in the latter group 1 min after commencement of CPR and was deflated within 1 min after ROSC. Systemic blood pressures, cerebral cortical blood flow, cerebral tissue pH and PCO2 were monitored continuously and the cerebral oxygen extraction ratio was calculated. RESULTS: During CPR, arterial blood pressure and cerebral perfusion pressure were greater in the balloon-vasopressin group, as compared with the IV-vasopressin group. These pressures did not differ between the groups after ROSC. Cerebral cortical blood flow was not significantly greater in the balloon-vasopressin group during CPR, whereas significantly higher cortical blood flow levels were recorded after ROSC. Cerebral tissue pH decreased in the IV-vasopressin group during the post-resuscitation hypoperfusion period. In contrast, decreasing pressures during the hypoperfusion period did not result in increasing tissue acidosis in the balloon-vasopressin group. CONCLUSIONS: During CPR, intra-aortic vasopressin combined with aortic balloon occlusion resulted in significantly greater perfusion pressures but not in greater cerebral cortical blood flow. After ROSC, however, a greater increase in cortical blood flow was recorded in the balloon-vasopressin group, even though the aortic balloon was deflated and perfusion pressures did not differ between the groups. This suggests that vasopressin predominantly gives vasoconstrictive effects on cerebral cortical vessels during CPR, but results in cerebral cortical vasodilatation after ROSC.

Animals↗
PubMed1986

Specific vasopressin binding to rat adrenal glomerulosa cells. Relationship to inositol lipid breakdown.

Cells from the zona glomerulosa of rat adrenals were isolated and maintained for 3 days in primary culture. Specific vasopressin binding was determined by using [3H]vasopressin. [3H]Vasopressin binding was time-dependent (half-time of about 2 min for 6 nM free ligand) and reversible on addition of unlabelled vasopressin (80% dissociation within 30 min). Dose-dependent [3H]vasopressin binding at equilibrium indicated that vasopressin interacted with two populations of sites: high-affinity sites (dissociation constant, Kd = 1.8 nM; maximal binding capacity = 10 fmol/10(6) cells) and low-affinity sites. Vasopressin increased the cellular content of labelled inositol mono-, bis- and tris-phosphate in cells prelabelled with myo-[3H]inositol. The vasopressin concentration eliciting half-maximal inositol phosphate accumulation was very close to the Kd value for vasopressin binding to high-affinity sites. Competition experiments using agonists and antagonists with enhanced selectivity for previously characterized vasopressin receptors indicated that vasopressin receptors from rat glomerulosa cells are V1 receptors of the vascular or hepatic subtype. The detected specific vasopressin-binding sites might represent the specific receptors mediating the mitogenic and steroidogenic effects of vasopressin on glomerulosa cells from rat adrenals.

Adrenal Glands↗
PubMed1997

Excitatory and inhibitory actions of vasopressin on colonic excitation-contraction coupling in dogs.

BACKGROUND & AIMS: Vasopressin, a circulating hormone and agent used to treat gastrointestinal bleeding, affects gastrointestinal motility. Both excitatory and inhibitory responses that may be caused by species differences or concentration-dependent effects of this hormone have been reported. This study examined the actions of vasopressin on the canine colon and studied the mechanism underlying the excitatory effects of vasopressin. METHODS: Intracellular microelectrodes and isometric force measurements were used to measure vasopressin responses in muscle strips. The patch-clamp technique was used to record arginine vasopressin activation of nonselective cation currents in isolated myocytes. RESULTS: Vasopressin (10(-12) to 10(-9) mol/L) increased electrical slow waves and enhanced phasic contractions. Atropine and tetrodotoxin did not alter the responses to vasopressin. In myocytes, vasopressin activated a nonselective cation conductance at concentrations that enhanced slow waves. Vasopressin (> 5 x 10(-8) mol/L) caused a tetrodotoxin- or NG-nitro-L-arginine methyl ester-insensitive inhibition of slow waves and contractile activity. A V1-receptor antagonist shifted the effects of vasopressin to higher concentrations. Immunohistochemistry showed expression of vasopressin-like immunoreactivity within the colonic wall, suggesting that local concentrations may exceed circulating levels. CONCLUSIONS: These data document the concentration dependence of the biphasic effects of vasopressin and provide a mechanism for the excitatory effects of vasopressin at physiological levels.

Acetylcholine↗
PubMed1999

The effects of vasopressin on endotoxin-induced attenuation of contractile responses in human gastroepiploic arteries in vitro.

UNLABELLED: We studied the effects of vasopressin on contraction in normal and endotoxin-treated human gastroepiploic arterial rings in vitro. In this tissue, vasopressin (50-500 pg/mL) produced concentration-dependent, endothelium-independent contractions. Vasopressin also potentiated the contraction elicited by 1.0 micromol/L norepinephrine (NE) in both the presence and absence of endothelium. Endotoxin (10 microg/mL) attenuated the 1.0 micromol/L NE-induced contractions, and this attenuation was reversed by 300 micromol/L N(G)-nitro-L-arginine-methyl ester (L-NAME) and by 300 micromol/L N(G)-nitro-L-arginine (L-NoArg). After 12 h endotoxin treatment, the vasopressin-induced contraction was attenuated, and the enhancing effect of vasopressin was diminished. However, both before and after endotoxin, the enhancement produced by vasopressin was larger than the vasopressin-contraction itself. An antagonist of the vasopressin V1 receptor, 1.0 micromol/L beta-mercapto-[beta,beta-cyclopentamethylenpropionyl1,O-MeTyr2+ ++,Arg8]-vasopressin, and an antagonist of V1 + V2 receptor receptor, 1.0 micromol/L des-Gly9-[beta-mercapto-beta,beta-cyclopentamethylenepropionyl1 ,O-Et-Tyr2,Val,Arg8]-vasopressin, each diminished the vasopressin-induced enhancement of the NE contraction. IMPLICATIONS: The results of our study suggest that, in addition to its direct vasoconstrictor effect, vasopressin strongly enhances the responses to norepinephrine through V1-receptor stimulation and that vasopressin could find a role in the management of endotoxin-induced vasodilation.

Adult↗
PubMed2007

Milrinone combined with vasopressin improves cardiac index after cardiopulmonary resuscitation in a pig model of myocardial infarction.

BACKGROUND: Milrinone used for acute cardiac insufficiency could be of interest during cardiopulmonary resuscitation because of its positive inotropic effects. In this study, the combination of milrinone-vasopressin was compared with epinephrine and vasopressin, as well as with the combination of epinephrine-vasopressin, in reference to hemodynamics. METHODS: Thirty-two pigs underwent ligation of the circumflex coronary artery and induction of ventricular fibrillation lasting for 4 min. Cardiopulmonary resuscitation was performed after randomization to one of four groups: epinephrine (30-microg/kg bolus), vasopressin (0.4-U/kg bolus), epinephrine-vasopressin (15-microg/kg epinephrine bolus, 0.2-U/kg vasopressin bolus), or milrinone-vasopressin (0.4-U/kg vasopressin bolus, 50-microg/kg milrinone bolus over 5 min and a continuous infusion of 0.4 microg.kg.min). The hemodynamic variables were measured before cardiopulmonary resuscitation as well as 4, 8, 15, and 30 min after return of spontaneous circulation. RESULTS: All animals were resuscitated successfully. The animals of the milrinone-vasopressin group displayed significantly (P<0.05) higher cardiac index values (30 min after return of spontaneous circulation: epinephrine, 65.8+/-13.2; vasopressin, 70.7+/-18.3; epinephrine-vasopressin, 69.1+/-36.2; milrinone-vasopressin, 120.7+/-34.8 ml.min.kg) without a decrease in mean arterial pressure or coronary perfusion pressure. CONCLUSIONS: The combination of vasopressin-milrinone as compared with epinephrine during cardiopulmonary resuscitation leads to an improved cardiac index without relevant decrease of mean arterial pressure or coronary perfusion pressure.

Animals↗
PubMed2006

Decreased vasopressin responsiveness in vasodilatory septic shock-like conditions.

OBJECTIVE: To determine the effect of vasodilatory septic shock-like conditions on vasoconstricting responses to vasopressin and norepinephrine in isolated resistance arteries. DESIGN: Prospective, randomized animal study. SETTING: University research laboratory. SUBJECTS: Male adult Sprague-Dawley rats. INTERVENTIONS: Small mesenteric arteries (outside diameter, 50-150 microm) were cannulated and studied in vitro under physiologic conditions. A vasodilatory septic shock-like state was produced by treatment with the nitric oxide (NO) donor, S-nitroso-N-acetylpenicillamine (SNAP), and the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine (IBMX). Vasoconstricting concentration-response relationships were determined for norepinephrine and vasopressin before and after application of SNAP or SNAP+ IBMX. Synergism between low-dose vasopressin and norepinephrine and between low-dose norepinephrine and vasopressin was determined before and after SNAP or SNAP+IBMX. MAIN RESULTS: Norepinephrine and vasopressin produced concentration-dependent contractions (half-maximal effective concentration [EC(50)] = 2.5 microM and 3.9 nM, respectively) that were significantly inhibited by 1 microM SNAP (EC(50) = 3.6 microM and 8.1 nM, respectively) or 100 microM SNAP + 10 microM IBMX (EC(50) = 10 microM and 8.2 nM, respectively). Low-dose vasopressin significantly increased the responsiveness to norepinephrine (EC50 = 0.5 microM) just as a low-dose norepinephrine significantly enhanced the vasopressin response (EC(50) = 2.3 nM). The synergistic effects of low-dose vasopressin and norepinephrine, or low-dose norepinephrine and vasopressin, were also significantly inhibited by 1 microM SNAP (EC(50) = 2.5 microM and 4.2 nM, respectively) or 100 microM SNAP + 10 microM IBMX (EC(50) = 9 microM and 8.4 nM, respectively). CONCLUSIONS: Vasoconstriction produced by vasopressin or norepinephrine, and the synergistic vasoconstriction produced by the combinations, was inhibited in vasodilatory septic shock-like conditions. Thus, in addition to the well-described vasopressin deficiency in vasodilatory septic shock, these studies indicate that decreased vasopressin responsiveness further contributes to a state of relative vasopressin insufficiency in this condition.

Animals↗
PubMed2005

Vasopressin may be useful in the treatment of systemic anaphylaxis in rabbits.

Recent studies demonstrate that vasopressin is useful when treating hemorrhagic and septic shock. The effect of vasopressin on systemic anaphylaxis has not been investigated except in clinical case reports. Vasopressin increases blood pressure because of vasoconstriction through the V1 receptor. Thus, we evaluated the effect of vasopressin on circulatory depression and bronchoconstriction provoked by systemic anaphylaxis and survival rates in rabbits. In the first set of experiments, 15 nonsensitized rabbits received normal saline (control) and vasopressin at 0.8 or 0.08 U/kg. In the second set, 40 sensitized rabbits received horse serum to induce anaphylaxis, and then received the same drugs as in the first set. In the first set, mean arterial pressure (MAP) in vasopressin groups increased by 18% to 24% compared with the control. Vasopressin at 0.8 U/kg decreased MAP insignificantly before the increases of MAP occurred. In the second set, vasopressin at 0.08 U/kg improved the survival rate. At 45 min after antigen challenge, 69% of the rabbits that received vasopressin at 0.08 U/kg were alive, whereas 29% of the control rabbits and 23% of the rabbits that received vasopressin at 0.8 U/kg were alive. Vasopressin increased MAP by 36% to 109% compared with the control within 5 min, however, at 2 min, vasopressin at 0.8 U/kg had no effect on MAP. Pulmonary dynamics were similar. In conclusion, vasopressin at 0.08 U/kg improved survival rates and severe hypotension provoked by systemic anaphylaxis, suggesting that this agent may be useful in the treatment of systemic anaphylaxis.

Anaphylaxis↗
PubMed1992

Effects on renal sodium and potassium excretion of vasopressin and oxytocin in conscious dogs.

Renal effects of arginine vasopressin and oxytocin were studied in conscious dogs, made water-diuretic by a waterload equivalent to 2% of body weight. Body water and content of sodium were maintained by separate servo-controlled infusions. Peptides were infused for 60 min at rates of 50 pg kg-1 min-1 (arginine vasopressin) or 1 ng kg-1 min-1 (oxytocin), either separately or combined. Infusions increased plasma arginine vasopressin to 1.9 +/- 0.2 (arginine vasopressin alone) and 1.8 +/- 0.3 pg kg-1 (arginine vasopressin plus oxytocin and plasma oxytocin to 72 +/- 5 (oxytocin alone) and 77 +/- 8 pg ml-1 (oxytocin plus arginine vasopressin). Arginine vasopressin or arginine vasopressin plus oxytocin increased urine osmolality similarly by a factor of 13, decreased urine flow to between 5 and 7% of control and decreased free water clearance. Oxytocin reduced urine flow and free water clearance and increased urine osmolality by a factor of 2. Oxytocin and arginine vasopressin separately increased excretion of sodium from 4 +/- 2 to 15 +/- 6 mumol min-1 and from 7 +/- 4 to 25 +/- 13 mumol min-1, respectively. Arginine vasopressin plus oxytocin led to a pronounced natriuresis (13 +/- 4 to 101 +/- 27 mumol min-1). Arginine vasopressin and arginine vasopressin plus oxytocin increased the excretion of potassium by a factor of 2.5. Oxytocin and arginine vasopressin plus oxytocin increased urinary Na+/K+ ratio by a factor of 3.7.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Gadolinium ions inhibit exocytotic vasopressin release from the rat neurohypophysis.

Single rat neurointermediate lobes (n.i.l.s) were fixed by their stalks to a platinum wire clip electrode and incubated in oxygenated Krebs-HEPES medium. Vasopressin release int the medium was determined by radioimmunoassay. Vasopressin secretion was increased by different stimuli and the effects of gadolinium (Gd3+) were tested. Electrical stimulation (15 Hz, three times 1 min with 1 min intervals) increased vasopressin release in a calcium-dependent manner. Gd3+ (10 microM to 3 mM) inhibited the evoked release of vasopressin in a concentration-dependent fashion; at 3 mM the inhibition was 98%. The inhibitory effect of Gd3+ up to 300 microM was antagonized by increasing the calcium concentration in the medium up to 6 mM. The effects of 1 and 3 mM-Gd3+ were unaffected by increasing the calcium concentration. Exposure of n.i.l.s to depolarizing concentrations of potassium (high K+, 60 mM, 30 min) increased the vasopressin release more than 33-fold. The elevated vasopressin release remained constant during six consecutive 5 min periods. In the initial 5 min period 300 microM-Gd3+ reduced the evoked vasopressin release by 80% but during the last 5 min period only by 30%. At 3 mM-Gd3+ vasopressin release was completely blocked during the whole time of incubation with high K+. Vasopressin release induced by exposure of n.i.l.s to cold (4 degrees C, 20 min) was completely inhibited by 3 mM-Gd3+, but reduced by only 25% in the presence of 300 microM-Gd3+. Vasopressin release induced by incubation of n.i.l.s with the ionophore X-537A (lasalocid) (10 microM, 30 min) was reduced by 90% in the presence of 300 microM-Gd3+ and completely prevented by 3 mM-Gd3+. 300 microM-Gd3+, added to the incubation medium, had no significant effect on the vasopressin release from crude synaptosomal preparations evoked by high K+. However, when 300 microM-Gd3+ was already present during the tissue homogenization, the evoked vasopressin release from the synaptosomes was completely blocked. It is concluded that Gd3+ inhibits exocytotic vasopressin release at two different sites. First, Gd3+ may block voltage-regulated calcium channels. Secondly, Gd3+ may inhibit the exocytotic release mechanism by an intracellular site of action. It is speculated that contractile proteins may be the intracellular target for Gd3+.

Animals↗
PubMed1989

Role of renal nerves in the potentiation of atriopeptin-induced natriuresis by vasopressin.

Previous studies have shown that vasopressin potentiates the natriuresis produced by atriopeptin. In five anesthetized dogs of this study, we found that the potentiation was proportional to the dose of vasopressin infused. Sodium excretion was 46 +/- 16 mueq/min with atriopeptin (103-126) (AP24) alone (0.36 nmol/kg.min), was increased to 127 +/- 29 by concomitant intravenous infusion of 0.4 mU/kg.min vasopressin, was further increased to 301 +/- 75 by 1.2 mU/kg.min vasopressin and leveled off at 328 +/- 37 with 3.6 mU/kg.min vasopressin. To investigate whether the potentiation by vasopressin was due to an intrarenal action, we infused three doses of vasopressin (0.04, 0.12, and 0.36 mU/kg.min) into the renal artery during intravenous AP24 infusion in a second group of five dogs. The natriuresis, 128 +/- 18 mueq/min, was unaffected by any intrarenal dose of vasopressin. In a third group, we determined whether the potentiation produced by vasopressin was mediated by a mechanism involving the renal nerves by denervating the left kidney before AP24 infusion. In the denervated kidneys, sodium excretion was increased from a control value of 33 +/- 5 mueq/min to 303 +/- 38 with AP24 alone and was unresponsive to subsequent intravenous vasopressin administration. The exaggerated natriuresis with AP24 alone was of the same magnitude as that produced by AP24 plus the highest doses of intravenous vasopressin in the innervated kidneys of the first group. From these results we conclude that the potentiation of AP-induced natriuresis by vasopressin is mediated by a mechanism involving the renal nerves and probably results from the known effect of vasopressin to inhibit renal nerve activity.

Animals↗
PubMed1968

Norepinephrine inhibition of vasopressin antidiuresis.

The effect of norepinephrine on exogenous vasopressin antidiuresis was investigated in water-loaded subjects. After an initial 2 to 3 hr period of water loading (phase 1), 10-100 mU of vasopressin per hr were infused at a constant rate for 1 hr (phase 2) followed by infusion of 10-100 mU of vasopressin per hr plus 600 mug of l-norepinephrine per hr for 1 hr (phase 3). Endogenous creatinine clearance, osmolal clearance, and free water clearance (in milliliters/minute) and sodium and chloride excretion (in milliequivalents/minute) were measured. In 10 subjects given 10-20 mU of vasopressin per hr during phases 2 and 3, free water clearance decreased significantly from phase 1 to phase 2 (9.3 to 0.15, P = 0.001) and increased during phase 3 norepinephrine infusion to 4.7 ml/min (P = 0.001). A comparable decrease in phase 2 free water clearance was observed in four subjects given 50 or 100 mU of vasopressin per hr during phases 2 and 3 (P < 0.01); however, the phase 3 norepinephrine infusion in these subjects was not associated with an increase in free water clearance. Creatinine clearance, osmolal clearance, and sodium and chloride excretion were unchanged throughout the studies in both groups of subjects.A two phase study in seven subjects confirmed that 10, 20, or 75 mU of vasopressin per hr susstained antidiuresis during phase 2 for at least 2 hr and that free water clearance values were essentially constant in the individual subject after the first 30 min of infusion. The magnitude of the (phase 3) norepinephrine-induced increase in free water clearance (4.5 +/- 0.64 ml/min) during infusion of 10-20 mU of vasopressin per hr, the failure of norepinephrine to increase free water clearance during infusion of 50-100 mU of vasopressin per hr, and the relatively constant endogenous creatinine and osmolal clearance rates would suggest that the norepinephrine inhibition of vasopressin antidiuresis was not the result of alterations in renal blood flow. A post-phase 3 infusion of vasopressin in four subjects resulted in a marked decrease in free water clearance, indicating that the norepinephrine inhibition of vasopressin antidiuresis was not accountable on the basis of decreased medullary hypertonicity. These data support the hypothesis that catecholamine blocks the cellular mechanism of vasopressin antidiuresis in vivo. The observation that norepinephrine did not inhibit the antidiuresis produced by the infusion of 50 or 100 mU of vasopressin per hr suggests that this inhibition might be competitive. A possible role of catecholamine in the mechanism of cold diuresis is suggested.

Adult↗
PubMed1997

Role of cyclic nucleotides in vasopressin-induced piglet pial artery dilation and opioid release.

It has previously been observed that the opioids methionine enkephalin and leucine enkephalin contribute to hypoxia-induced pial artery dilation in the piglet. It has also been demonstrated that vasopressin elicits pial artery dilation and contributes to hypoxia-induced pial dilation both directly and indirectly through the release of the above opioids. The present study was designed to investigate the role of cyclic nucleotides in this vasopressin-induced pial artery dilation and opioid release in newborn piglets equipped with a closed cranial window. Pial artery diameter and cortical periarachnoid cerebrospinal fluid (CSF) opioid and cyclic nucleotides were measured after topical application of vasopressin (40, 400, and 4000 pg/mL). Opioid levels and pial diameter were examined in the absence and presence of (Rp)-8-bromo-(Br)-cAMPs and (Rp)-8-Br-cGMPs, purported cAMP and cGMP antagonists, respectively. Periarachnoid cortical CSF cAMP concentration increased in response to topical vasopressin (1048 +/- 22, 1199 +/- 51, 1334 +/- 61 and 1453 +/- 59 fmol/mL for control, 40, 400, and 4000 pg/mL vasopressin, respectively, n = 9). Vasopressin elicited pial artery dilation, which was attenuated by (Rp)-8-Br-cAMPs (14 +/- 1, 22 +/- 1, and 29 +/- 2 versus 8 +/- 1, 12 +/- 2, and 18 +/- 2% dilation for 40, 400, 4000 pg/mL vasopressin, before and after (Rp)-8-Br-cAMPs, respectively, n = 7). Similarly, vasopressin-induced pial artery dilation was accompanied by elevated CSF cGMP and this dilation was attenuated in the presence of (Rp)-8-Br-cGMPs (13 +/- 1, 21 +/- 1, and 29 +/- 2 versus 5 +/- 1, 9 +/- 1, and 12 +/- 1% dilation for 40, 400, and 4000 pg/mL vasopressin before and after (Rp)-8-Br-cGMPs, respectively, n = 7). CSF opioid concentrations increased with topical vasopressin and these increases were attenuated by (Rp)-8-Br-cAMPs. CSF methionine enkephalin concentrations were 1193 +/- 60, 1530 +/- 63, 1937 +/- 89, and 2422 +/- 104 versus 1032 +/- 25, 1185 +/- 261, 1337 +/- 31, and 1519 +/- 44 pg/mL for control, 40, 400 and 4000 pg/mL vasopressin before and after (Rp)-8-Br-cAMPs. Similarly, vasopressin-induced CSF methionine enkephalin and leucine enkephalin release was attenuated in the presence of (Rp)-8-Br-cGMPs. These data show that both cAMP and cGMP contribute to vasopressin-induced pial artery dilation and the release of the opioids methionine enkephalin and leucine enkephalin.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1985

Cerebrospinal fluid and plasma vasopressin in the fetal lamb: basal concentration and the effect of hypoxia.

The concentrations of vasopressin in the plasma and cerebrospinal fluid (CSF) of the chronically catheterized fetal lamb were measured under basal and hypoxic conditions. Under basal conditions, samples were obtained from 13 fetal lambs of 117-146 days gestation. The mean +/- SEM vasopressin level in CSF was 19.5 +/- 1.5 pg/ml; the mean plasma vasopressin level of 1.9 +/- 0.2 pg/ml was significantly less (P less than 0.001). No consistent change in concentrations of vasopressin in CSF was observed with gestational maturation in 3 animals sampled sequentially or in individual samples obtained over the last 32 days of gestation. The mean vasopressin concentration in the CSF of the pregnant ewe was 5.1 +/- 0.4 pg/ml. The gradients for osmolality, sodium, and potassium between fetal plasma and CSF were: osmolality, 298.4 +/- 1.6 to 304.3 +/- 1.4 mosmol/kg; sodium, 140.9 +/- 0.5-142.5 +/- 0.5 meq/liter; and potassium, 4.3 +/- 0.1 to 3.3 +/- 0.1 meq/liter. Fetal hypoxia was induced by exposure of the ewe to 10% O2 in N2 for 30 min. The concentration of vasopressin increased from 1.7 +/- 0.3 to 277 +/- 144 pg/ml (P less than 0.001) in fetal plasma and from 21.4 +/- 3.8 to 47.1 +/- 9.9 pg/ml (P less than 0.04) in fetal CSF. When the ewe was exposed to room air under comparable experimental conditions, no similar changes in plasma or CSF vasopressin levels were observed in the fetus. Infusion of vasopressin into the fetal jugular vein at 1.0 mU/min for 30 min increased plasma concentrations from 2.3 +/- 0.5 to 83 +/- 17 pg/ml, while the CSF vasopressin values were 31.9 +/- 5.9 (basally) and 30.7 +/- 4.8 pg/ml (after infusion). Mean plasma and CSF osmolality, sodium, and potassium were not changed by any of these experimental interventions. We conclude that 1) under basal conditions, high concentrations of vasopressin are present in the CSF of the fetal lamb, the blood-CSF barrier appears to be impermeable to vasopressin, and concentrations of the hormone in fetal plasma are less than those in CSF; and 2) hypoxia is a potent stimulus of vasopressin release in both fetal plasma and CSF. The route of vasopressin released into the fetal CSF may be distinct from that released into plasma.

Animals↗
PubMed1986

Area postrema lesions augment the pressor activity of centrally administered vasopressin.

The effects of arginine vasopressin given into either the vertebral arteries, a peripheral vein (IV), or the cisterna magna of 15 morphine-chloralose anesthetized dogs were measured before and after pharmacological blockade with the antagonist [d(CH2)5 Tyr(Me) AVP]. The contribution of the area postrema to the pressor activity of vasopressin was assessed in nine other dogs by comparing the responses to vasopressin before and after surgical ablation of this structure. Administration of vasopressin either via the vertebral arteries or intravenously produced comparable gradual rises in blood pressure, accompanied by bradycardia and decreases in the plasma levels of norepinephrine. Administration of intracisternal vasopressin elicited a smaller rise in arterial pressure, tachycardia, and increases in plasma norepinephrine levels. The pressor and bradycardic effects of IV vasopressin were abolished when the antagonist was given via the same route. In contrast, intravertebral infusion of the vasopressin antagonist caused tachycardia and modest hypotension in response to intravenous or intravertebral infusions of vasopressin. Pressor effects of vasopressin given into the cisterna magna were not altered by systemic delivery of the vasopressin blocker. Removal of the area postrema selectively augmented the pressor effects of intravertebral vasopressin, whereas the pressor activity of IV vasopressin remained unchanged. These findings provide new evidence for an action of circulating vasopressin in cardiovascular regulation, mediated in part by the area postrema.

Animals↗
PubMed1996

Role of endothelin in pial artery vasoconstriction and altered responses to vasopressin after brain injury.

Pial artery constriction following fluid-percussion injury to the brain is associated with elevated cerebrospinal fluid (CSF) vasopressin concentration in newborn pigs. It has also been observed that fluid-percussion injury reverses the function of vasopressin from that of a dilator to a constrictor. Endothelin-1 (ET-1), a purported mediator of cerebral vasospasm, can be released by several stimuli, including vasopressin. The present study was designed to investigate the role of ET-1 in pial artery constriction and in the reversal of vasopressin from a dilator to a constrictor, which is observed after fluid-percussion injury. Brain injury of moderate severity (1.9-2.3 atm) was produced in anesthetized newborn pigs that had been equipped with a closed cranial window. Endothelin-1 elicited pial dilation at low concentrations and vasoconstriction at higher concentrations. Fluid-percussion injury reversed the process of dilation to that of constriction at the low ET-1 concentration and potentiated this constriction at high ET-1 concentrations (10% +/- 1%, -8% +/- 1%, and -15% +/- 1% vs. -6% +/- 1%, -17% +/- 1%, and -26% +/- 2% for 10(-12), 10(10),10(-8) M ET-1 before and after fluid-percussion injury, respectively). Vasopressin modestly increased CSF ET-1 concentration before fluid-percussion injury. Fluid-percussion injury markedly increased CSF ET-1 concentration and the ability of vasopressin to release ET-1 (20 +/- 2, 26 +/- 3, and 40 +/- 4 pg/ml vs. 93 +/- 6, 141 +/- 9, and 247 +/- 31 pg/ml for control, 40 pg/ml vasopressin, and 400 pg/ml vasopressin before and after fluid-percussion injury, respectively). An ET-1 antagonist, BQ 123 (10(-6) M) blunted pial artery constriction following fluid-percussion injury (146 +/- 5 microns -127 +/- 6 microns vs.144 +/- 5 microns-136 +/- 4 microns). The BQ 123 also blocked the reversal of vasopressin's function from that of a dilator to a constrictor after fluid-percussion injury (8% +/- 1%, 21% +/- 3%, and -5% +/- 1%, -14% +/- 2% vs. 8% +/- 1%, 21% +/- 2% and 4% +/- 1%, 2% +/- 1% for 40 and 4000 pg/ml vasopressin before and after fluid-percussion injury in the absence and presence of BQ 123, respectively). The BQ 123 blocked the constrictor component to ET-1, whereas it had no effect on the dilator component. These data show that ET-1 contributes to pial constriction after fluid-percussion injury. These data also indicate that vasopressin-induced release of ET-1 contributes to the reversal of vasopressin from a dilator to a constrictor following fluid-percussion injury. Furthermore, these data indicate that elevated CSF vasopressin and ET-1 interact in a positive feedback manner to promote pial artery constriction following fluid-percussion injury.

Animals↗
PubMed1994

Aggregation of vasopressin mRNA in a subset of axonal swellings of the median eminence and posterior pituitary: light and electron microscopic evidence.

The mRNA encoding vasopressin has recently been documented within the magnocellular hypothalamo-neurohypophyseal projections of the rat such as the median eminence (ME) and the posterior pituitary (PP), suggesting the possibility of its axonal transport. To address the origin of this mRNA and to investigate the functional significance of this unexpected axonal transport of mRNA, we have examined its subcellular localization within both magnocellular perikarya and their axonal projections. For this purpose, we have used nonradioactive in situ hybridization techniques in order to localize the vasopressin mRNA with precision at the ultrastructural level in magnocellular perikarya, dendrites, and axons from control, salt-loaded, and lactating rats. This approach permitted us to demonstrate directly the axonal localization of vasopressin mRNA. Moreover, we were able to obtain novel information concerning vasopressin mRNA compartmentation within both perikarya and axons. At both light and electron microscopic levels, we observed vasopressin mRNA-containing cells in the hypothalamic magnocellular cell body groups, but not in the ME or in the PP. When vasopressin mRNA was detected in medium-size dendrites, it was always associated with the rough endoplasmic reticulum (RER). Within the labeled magnocellular perikarya, the abundant vasopressin mRNA was mainly associated with discrete areas of the RER. However, vasopressin mRNA was never detected in the Golgi apparatus or in association with neurosecretory granules, in perikarya or axons. These data suggest that vasopressin mRNA translation is restricted to certain segments within the RER, and that axonal transport of vasopressin mRNA does not involve the classical neurosecretory pathway, via the Golgi apparatus and the neurosecretory granules, as has been proposed. Within the magnocellular neuron axons, vasopressin mRNA could be detected only in a subset of axonal swellings, all of which were confined to the internal layer of the ME and the PP. The mRNA-containing swellings were numerous in 7 d salt-loaded animals, less abundant in lactating animals, and almost undetectable in control animals. In all groups of animals, no vasopressin mRNA was detectable in any other region of the magnocellular neuron axons, including undilated axonal segments or varicose swellings. These results strongly suggest that, under physiological activation such as chronic salt loading, axonal vasopressin mRNA is increased and becomes aggregated in a selected subset of swellings of the ME and the PP. Furthermore, these data indicate that along the magnocellular neuron axons, the swellings may differ in their biochemical and functional features. Further analysis focused on the mRNA-accumulating swellings may illuminate the function of RNA within the axonal compartment.

Animals↗
PubMed1994

Vasopressin-induced calcium signaling in cultured hippocampal neurons.

We recently demonstrated that the neural peptide vasopressin (AVP) can act as a neurotrophic factor for hippocampal nerve cells in culture. Because the neurotrophic effect of vasopressin is mediated by the V1 receptor, we investigated AVP activation of calcium signaling pathways in cultured hippocampal neurons. Results of this investigation demonstrate that exposure of cultured hippocampal neurons prelabeled with [3H]myo-inositol to vasopressin induced a significant accumulation of [3H]inositol-1-phosphate ([3H]IP1). The selective V1 vasopressin receptor agonist, [Phe2, Orn2]vasotocin, induced a significant accumulation of [3H]IP1 whereas a selective V2 vasopressin receptor agonist, [deamino1, D-Arg8]-vasopressin, did not. Moreover, V1 agonist-induced accumulation of [3H]IP1 was blocked by the selective V1 vasopressin receptor antagonist d(CH2)5[Tyr(Me)2]-vasopressin. V1 agonist-induced accumulation of [3H]IP1 was concentration dependent and exhibited a steep inverted U-shaped curve that included both stimulation and inhibition of [3H]IP1 accumulation. Time course analysis of V1 agonist-induced accumulation of [3H]IP1 revealed significant increase by 20 min which continued to be significantly elevated for 60 min. Investigation of the effect of closely related peptides on [3H]IP1 accumulation indicated that the vasopressin metabolite peptide AVP4-9 and oxytocin significantly increased [3H]IP1 accumulation whereas the vasopressin metabolite peptide AVP4-8 did not. AVP4-9 and oxytocin induced [3H]IP1 accumulation were blocked by the V1 vasopressin receptor antagonist d(CH2)5[Tyr(Me)2]-vasopressin. V1 receptor activation was associated with a pronounced rise in intracellular calcium. Results of calcium fluorometry studies indicated that V1 agonist exposure induced a marked and sustained rise in intracellular calcium that exhibited oscillations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Vasopressin-induced calcium signaling in cultured hippocampal neurons.

We recently demonstrated that the neural peptide vasopressin (AVP) can act as a neurotrophic factor for hippocampal nerve cells in culture. Because the neurotrophic effect of vasopressin is mediated by the V1 receptor [11], we investigated AVP activation of calcium signaling pathways in cultured hippocampal neurons. Results of this investigation demonstrate that exposure of cultured hippocampal neurons prelabeled with [3H]myo-inositol to vasopressin induced a significant accumulation of [3H]inositol-1-phosphate ([3H]IP1). The selective V1 vasopressin receptor agonist, [Phe2, Orn2]vasotocin, induced a significant accumulation of [3H]IP1 whereas a selective V2 vasopressin receptor agonist, [deamino1, D-Arg8]-vasopressin, did not. Moreover, V1 agonist-induced accumulation of [3H]IP1 was blocked by the selective V1 vasopressin receptor antagonist d(CH2)5[Tyr(Me)2]-vasopressin. V1 agonist-induced accumulation of [3H]IP1 was concentration dependent and exhibited a steep inverted U-shaped curve that included both stimulation and inhibition of [3H]IP1 accumulation. Time course analysis of V1 agonist-induced accumulation of [3H]IP1 revealed significant increase by 20 min which continued to be significantly elevated for 60 min. Investigation of the effect of closely related peptides on [3H]IP1 accumulation indicated that the vasopressin metabolite peptide AVP4-9 and oxytocin significantly increased [3H]IP1 accumulation whereas the vasopressin metabolite peptide AVP4-8 did not. AVP4-9 and oxytocin induced [3H]IP1 accumulation were blocked by the V1 vasopressin receptor antagonist d(CH2)5[Tyr(Me)2]-vasopressin. V1 receptor activation was associated with a pronounced rise in intracellular calcium. Results of calcium fluorometry studies indicated that V1 agonist exposure induced a marked and sustained rise in intracellular calcium that exhibited oscillations.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗