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PubMed1985

Activation of human blood platelets by arginine-vasopressin. Role of bivalent cations.

Arginine-vasopressin caused platelet activation, i.e., a shape change reaction and a rise in intracellular free Ca2+ ([Ca2+]i) only in the presence of certain bivalent cations. The EC50 of arginine-vasopressin (concentration causing half-maximal shape change) decreased with rising concentrations of Mn2+, Mg2+, or Ca2+ in the medium, but was at least an order higher with Ca2+ than with Mn2+ or Mg2+. The EC50 of the active bivalent cations (concentrations enabling 100 nM arginine-vasopressin to exert half-maximal shape change and rise in [Ca2+]i) varied with the individual cations, being by far the highest for Ca2+. The KD of [3H]arginine-vasopressin binding to platelet membranes and intact platelets markedly decreased when extracellular Mg2+ or Mn2+ were present, and the KD values were inversely related to the concentration of the cations. Ca2+ also lowered the KD values; however, the effect was less marked than that of Mg2+ or Mn2+ and, in physiological conditions, significant only in intact platelets. Vasopressin-1 antagonists counteracted arginine-vasopressin binding and the shape change reaction and [Ca2+]i rise induced by arginine-vasopressin. In the presence of Mn2+ in the medium, administration of arginine-vasopressin led to quenching of the intracellular fluorescence of 2-methyl-6-methoxy-8-nitroquinoline-loaded platelets, possibly due to influx of Mn2+. In conclusion, the dependency of the arginine-vasopressin-induced platelet activation on bivalent cations is at least partly due to an enhancement by these cations of the affinity of the vasopressin-1 receptor for arginine-vasopressin. Thereby, under physiological conditions, Mg2+ seems to be of primary importance. Other mechanisms may be involved, too, e.g., an enhancement by arginine-vasopressin of the influx of bivalent cations into the platelets.

Aminoquinolines↗
PubMed1994

The effects of [Arg8]vasopressin and [Arg8]vasotocin on the firing rate of suprachiasmatic neurons in vitro.

The excitatory effect of [Arg8]-vasopressin and its potential contribution to the circadian cycle of electrical activity in the suprachiasmatic nucleus of the rat was investigated using extracellular recordings from hypothalamic slices from virgin female rats. The majority of neurons tested for their responses to vasopressin and [Arg8]-vasotocin displayed coincident, dose-dependent excitation by both peptides, although the relative efficacy varied between neurons, with some showing a highly preferential excitation by vasotocin. Perifusion with the vasopressin receptor antagonist d(CH2)5[Tyr(OEt)2,Val4,Cit8]-vasopressin was able to block the majority of responses to vasopressin or vasotocin (20/25), and similar excitation could be induced by the selective agonist [Phe2,Orn8]-vasotocin, indicating a mainly V1 receptor-mediated effect. Few neurons (3/27; 11%) responded to the oxytocin-specific agonist, [Thr4,Gly7]-oxytocin, suggesting a low occurrence of oxytocin receptors. In addition to blocking the action of exogenous vasopressin, the V1 antagonist caused a reversible suppression of spontaneous basal activity in 7/25 cases, consistent with the presence of an endogenous excitatory vasopressin tone. In agreement with previous reports, the activity of suprachiasmatic nucleus neurons showed a significant correlation between spontaneous activity and the light-dark cycle, with activity decreasing during the subjective dark phase. When neurons were divided on the basis of their response to vasopressin and/or vasotocin, the peptide-sensitive neurons continued to show a strong correlation (r = 0.513, P < 0.01) while the insensitive neurons showed no correlation (r = 0.136, P > 0.05). These data confirm the presence of V1 type receptors in the suprachiasmatic nucleus and also indicate a small number of neurons possessing additional classes of receptor selective for either oxytocin or vasotocin. Contrary to previous reports, they also demonstrate that endogenous vasopressin tonically excites suprachiasmatic nucleus neurons. The fact that vasopressin-sensitive (but not vasopressin-insensitive) neurons show a level of basal activity correlated with time, suggests that this tone may contribute to the circadian cycle of electrical activity in the suprachiasmatic nucleus.

Action Potentials↗
PubMed1998

Vasopressin receptors involved in adrenergic neurotransmission in the circular muscle of the human vas deferens.

We studied the effects of vasopressin on the adrenergic responses of in vitro preparations of circular muscle from the vas deferens obtained from 28 men undergoing elective vasectomy. Vasopressin (3 x 10(-9)-3 x 10(-8) M) enhanced the phasic contractions elicited by electrical field stimulation and noradrenaline. This potentiation was blocked by the vasopressin V1 receptor antagonist d(CH2)5Tyr(Me)vasopressin (10(-6) M) but not by the vasopressin V2 receptor antagonist [d(CH2)5, D-Ile2,Ile4,Arg8]vasopressin (10(-6) M). The Ca2+ antagonist nifedipine (10(-6) M) did not affect the potentiation of electrical field stimulation induced by vasopressin and noradrenaline but reduced KCl-induced contractions and abolished the induction of phasic activity by vasopressin in the presence of KCl. The results demonstrate that vasopressin, in addition to its direct contractile effects, strongly potentiates contractions of human vas deferens elicited by adrenergic stimulation. Both the direct and indirect effects of vasopressin appear to be mediated by vasopressin V1 receptor stimulation and are independent of Ca2+ entry through dihydropyridine Ca2+ channels.

Adrenergic alpha-Agonists↗
PubMed2006

The vasopressin-induced excitation of hypoglossal and facial motoneurons in young rats is mediated by V1a but not V1b receptors, and is independent of intracellular calcium signalling.

As a hormone, vasopressin binds to three distinct receptors: V1a and V1b receptors, which induce phospholipase-Cbeta (PLCbeta) activation and Ca2+ mobilization; and V2 receptors, which are coupled to adenylyl cyclase. V1a and V1b receptors are also present in neurons. In particular, hypoglossal (XII) and facial (VII) motoneurons are excited following vasopressin-V1a receptor binding. The aim of the present study was double: (i) to determine whether V1b receptors contribute to the excitatory effect of vasopressin in XII and VII motoneurons; and (ii) to establish whether the action of vasopressin on motoneurons is mediated by Ca2+ signalling. Patch-clamp recordings were performed in brainstem slices of young rats. Vasopressin depolarized the membrane or generated an inward current. By contrast, [1-deamino-4-cyclohexylalanine] arginine vasopressin (d[Cha4]AVP), a V1b agonist, had no effect. The action of vasopressin was suppressed by Phaa-D-Tyr(Et)-Phe-Gln-Asn-Lys-Pro-Arg-NH2, a V1a antagonist, but not by SSR149415, a V1b antagonist. Thus, the vasopressin-induced excitation of brainstem motoneurons was exclusively mediated by V1a receptors. Light microscopic autoradiography failed to detect V1b binding sites in the facial nucleus. In motoneurons loaded with GTP-gamma-S, a non-hydrolysable analogue of GTP, the effect of vasopressin was suppressed, indicating that neuronal V1a receptors are G-protein-coupled. Intracellular Ca2+ chelation suppressed a Ca2+-activated potassium current, but did not affect the vasopressin-evoked current. H7 and GF109203, inhibitors of protein kinase C, were without effect on the vasopressin-induced excitation. U73122 and D609, PLCbeta inhibitors, were also without effect. Thus, excitation of brainstem motoneurons by V1a receptor activation is probably mediated by a second messenger distinct from that associated with peripheral V1a receptors.

Animals↗
PubMed1987

Evidence against a pressor role for vasopressin in spontaneous hypertension.

The hypothesis that the vasoconstrictor action of vasopressin may contribute to the development of hypertension in spontaneously hypertensive rats (SHR) was tested by chronic infusion of a specific antagonist of the vascular effects of vasopressin. From 4 to 13 weeks of age, SHR and Wistar-Kyoto rats (WKY) received subcutaneously either isotonic saline or the vasopressin pressor antagonist, d(CH2)5Tyr(Me)arginine vasopressin by osmopump. Systolic blood pressure was measured by tail cuff from 5 to 11 weeks of age. In SHR, the vasopressin analogue did not alter the rate or magnitude of increase in systolic blood pressure. In WKY, systolic blood pressure in the vasopressin analogue group was slightly reduced compared with the saline infusion values until 10 weeks of age (F1, 10 = 10.18, p = 0.008). At 12 to 14 weeks of age, all animals were prepared with indwelling arterial and venous catheters. Resting mean arterial pressure was not altered significantly by the vasopressin analogue infusion in either strain, but the response to an acute vasopressin infusion of 5, 15, or 50 ng/kg body weight was markedly attenuated by the analogue treatment, indicating that plasma levels of the vasopressin analogue were sufficient to block pressor effects of endogenous vasopressin. A bolus injection of the angiotensin II converting enzyme inhibitor teprotide (SQ 20881) resulted in a decrease in mean arterial pressure (p less than 0.05) that was comparable in all groups, and serum renin concentration was not elevated in the vasopressin analogue-treated rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Renal haemodynamic actions of pressor doses of lysine vasopressin in the rat.

1. Dose-response effects of lysine vasopressin on renal haemodynamics were studied in conscious rats infused with 2.5% (w/v) dextrose solution at 5.8 ml/h. 2. Lysine vasopressin was maximally antidiuretic in the absence of a significant pressor effect at a dose of 2.5 pmol h-1 100 g body weight-1. Doses of vasopressin greater than this induced a dose-dependent increase in arterial blood pressure. 3. The clearance of p-aminohippurate (PAH) was not significantly changed by vasopressin, even at pressor doses. Rats pre-treated with indomethacin to inhibit prostaglandin synthesis showed a decrease in PAH clearance during the infusion of vasopressin at a dose of 30 pmol h-1 100 g body weight-1, and this suggests that the renal vasoconstrictor actions of vasopressin are attenuated by dilator prostaglandins. 4. Inulin clearance was unchanged by non-pressor doses of vasopressin but was decreased in a dose-dependent manner by pressor doses. A maximal effect was induced by a dose of 30 pmol h-1 100 g body weight-1 which decreased inulin clearance from 3.23 +/- 0.76 (mean +/- S.E. of mean) to 1.60 +/- 0.37 ml/min (P less than 0.02). A change in inulin clearance (from 3.42 +/- 0.46 to 2.17 +/- 0.33 ml/min, P less than 0.01) was also observed in rats pre-treated with indomethacin and infused with vasopressin at the same dose. The magnitude of the change was not significantly different from that observed in rats which were not treated with indomethacin. 5. Control rats infused with dextrose showed a slight but significant increase in sodium excretion during the course of the experiment. A similar natriuresis was observed in rats infused with non-pressor doses of vasopressin but was considerably enhanced in rats infused with pressor doses of the peptide. The antidiuresis induced by vasopressin remained maximal in rats infused with pressor doses. 6. Potassium and osmolal outputs were unchanged by non-pressor doses of vasopressin but significantly increased during administration of pressor doses. 7. It is concluded that pressor doses of lysine vasopressin do not alter total renal perfusion in conscious rats when the prostaglandin system is intact. Glomerular filtration is, however, decreased in a dose-dependent manner by these amounts but the mechanism is unclear.

Animals↗
PubMed2001

Delayed effect of the vasopressin metabolite VP4-8 on the social memory of sexually naive male rats.

RATIONALE: Endogenous vasopressin is involved in the social memory of the male rat and administration of exogenous vasopressin improves social memory. These findings are mainly based on studies using sexually experienced males that were tested in the social recognition test. OBJECTIVE: The present study was aimed to establish whether the modulation of social memory by vasopressin fragments depends on the sexual experience of the male rat. For this purpose, the social discrimination test was used, since this test is more suitable than the social recognition test for measuring social memory in sexually naive males. METHODS: Male rats were tested in the social discrimination test and treated subcutaneously with the vasopressin metabolite [pGlu4,Cyt6]vasopressin-(4-8) (VP4-8). VP4-8 shares with vasopressin the effects on memory processes but lacks the peripheral effects of vasopressin. RESULTS: VP4-8 (1 microgram/kg) acutely improved the social memory of sexually experienced male rats, confirming previous reports. However, in sexually naive males VP4-8 failed to improve social memory in doses ranging from 0.1 microgram/kg to 1 microgram/kg. Instead, 1 microgram/kg VP4-8 or 6 micrograms/kg desglycinamide-vasopressin were found to exert a delayed effect in sexually naive rats. This delayed effect resulted in an improved social memory 2 days after administration. CONCLUSIONS: Vasopressin sensitisation is discussed as a possible underlying mechanism of the observed delayed effect of vasopressin fragments. It is concluded that in male rats sexual experience can influence the modulation of social memory by vasopressin.

Age Factors↗
PubMed1984

Interactions of vasopressin agonists and antagonists with membrane receptors.

Plasma membranes containing one class of non-cooperative binding sites for tritium-labelled [8-arginine]vasopressin were isolated from bovine kidney inner medulla and from rat liver. By using a weighted, non-linear least squares fit to logistic curves, the binding parameters of eight vasopressin agonists and antagonists were determined in competition experiments. Vasopressin analogues with sarcosine or N-methyl-L-alanine in position 7 instead of proline showed a high ratio of antidiuretic to vasopressor activity. These analogues retained a high binding affinity to the renal vasopressin receptor with apparent dissociation constants KD in the order proline less than sarcosine less than methylalanine . In contrast, the affinity to the hepatic vasopressin receptor, which shares characteristics with vasopressor receptors, was drastically reduced with KD values being in the order proline much less than N- methylalanine less than sarcosine. By combining the substitutions at position 7 with substitutions of cysteine in position 1 by either deaminopenicillamine or beta-mercapto-beta, beta-cyclopentamethylenepropionic acid, inhibitors of the oxytocoic and vasopressor responses were obtained. These additional substitutions at position 1 led to a drastic decrease in the binding affinity to the vasopressin receptor in bovine kidney. The intrinsic activity of these analogues to stimulate the renal vasopressin sensitive adenylate cyclase was strongly reduced or completely lost. In the rat liver system, however, these vasopressin antagonists showed a remarkably increased affinity to vasopressin receptors as compared to analogues substituted only at position 7. GTP reduced the binding affinity of all analogues to the hepatic receptor. The results show that these structural modifications which influence both the conformational properties of the vasopressin molecule and the biological activities of the hormone had strikingly different effects on the interactions of the resulting analogues with physiologically important receptors in the kidney and the liver. These studies may lead to the development of more specific vasopressin agonists and antagonists.

Adenylyl Cyclases↗
PubMed1996

Effect of luminal vasopressin on NaCl transport in the medullary thick ascending limb of the rat.

The aim of the present study was to determine whether vasopressin affects NaCl reabsorption in the medullary thick ascending limb of the loop of Henle when administered selectively to the luminal membrane. At 5 x 10(-6) M and 10(-8) M, luminal [Arg8]vasopressin significantly inhibited Cl- transport in the in vitro microperfused rat medullary thick ascending limb by 46.4 +/- 5.9% (P < 0.01) and 32.4 +/- 2.0% (P < 0.05) respectively. The response to 10(-8) M luminal [Arg8]vasopressin was completely blocked by the vasopressin V1 receptor antagonist [beta-mercapto-beta,beta-cyclopenta-methylenepropionyl1, O-Me-Tyr2,Arg8]vasopressin (10(-6) M), and was mimicked by the vasopressin V1 receptor agonist [Phe1, Ile5, Orn8]vasopressin (10(-8) M; delta -35.0 +/- 4.5%; P < 0.05). Luminal administration of the vasopressin V2 receptor agonist [deamino-Cys1, D-Arg8]vasopressin (5 x 10(-6) M) had no effect on transport. These data suggest that luminal vasopressin can inhibit NaCl transport in the medullary thick ascending limb of the rat via vasopressin V1 receptors.

Absorption↗
PubMed1985

24-hour cerebrospinal fluid levels of vasopressin in hydrocephalic patients.

The variation in vasopressin concentrations of ventricular cerebrospinal fluid and plasma throughout a 24-h period was studied in 10 patients with hydrocephalus. In 6 control patients, the diurnal variation in plasma vasopressin concentrations was studied. Vasopressin concentrations were determined by radioimmunoassay in plasma and in extracted and unextracted cerebrospinal fluid. Cortisol and osmolality in plasma were also measured. Vasopressin concentrations measured in extracted cerebrospinal fluid showed only small intra- and interindividual variation, while the corresponding values for unextracted cerebrospinal fluid were 2-5-fold higher and showed more variation. Plasma vasopressin concentrations varied considerably throughout the 24-h period in the individual hydrocephalic patient and between the patients. The pattern of variation was inconstant with no circadian rhythm, and the variation was not related to any changes in plasma osmolality, blood pressure or intracranial pressure. In some of the patients, the normal diurnal pattern of variation in plasma cortisol was broken, however, without a relation to the observed fluctuations in vasopressin concentrations. The abnormal variation of plasma vasopressin and cortisol was considered to reflect stress in connection with the intracranial pressure monitoring procedure. In the control patients, plasma vasopressin showed only small variations and plasma cortisol showed a normal diurnal rhythm. It is concluded that cerebrospinal fluid vasopressin concentration in patients with hydrocephalus is very constant throughout the day, even when plasma vasopressin concentrations show marked episodic increases. Thus, a circadian rhythm in the cerebrospinal fluid vasopressin concentration, as reported in several animal species, could not be confirmed in these patients.

Adult↗
PubMed2006

Vasopressin interactions with oxytocin in the control of female sexual behavior.

Previous studies have found that central administration of arginine vasopressin and arginine vasopressin receptor V1a antagonists respectively inhibited and stimulated receptivity but did not examine effects on other aspects of female sexual behavior. Central oxytocin facilitates both proceptive and receptive components of sexual behavior and diminishes male-directed agonistic behavior. The present study examined i.c.v.-administered arginine vasopressin and V1a antagonist effects on proceptive, receptive and agonistic behaviors, and interactions with oxytocin. In experiment 1, rats were primed s.c. with 2 microg estradiol benzoate x 2 days and with 500 microg of progesterone on day 3. Arginine vasopressin (0.2, 0.4 microg) or normal saline vehicle was administered 5 h after progesterone treatment and sexual and agonistic behavior measured 30, 60 and 90 min later. Compared with saline, both doses of arginine vasopressin significantly decreased lordosis responses to mounting and hop-dart proceptive behavior and trended toward significantly increasing agonistic behaviors. In experiment 2, oxytocin (2 microg) infusion just after arginine vasopressin (0.4 microg) significantly increased lordoses and decreased agonistic behaviors but did not affect hopping and darting. In experiment 3, conducted in ovariectomized rats primed with estradiol benzoate (1 microg/day s.c. x 2 days), i.c.v. infusion of 0.5 and 1.0 microg of the selective V1a antagonist, d(CH2)5Tyr-(Me)arginine vasopressin on day 3 significantly increased lordoses and trended toward increasing hopping and darting 4 and 6 h after i.c.v. treatment. In experiment 4, 1 microg of the selective oxytocin antagonist, d(CH2)5[Tyr(Me)2, Thr4, Tyr-NH2(9)]OVT given 1 h before d(CH2)5Tyr-(Me)arginine vasopressin (1 microg) significantly decreased lordoses. Previous studies indicate that arginine vasopressin contributes to light phase inhibition of female sexual behavior. Our findings suggest that arginine vasopressin may exert this effect through interactions that decrease oxytocin stimulation of sexual behavior and raise the question whether sex steroid conditions that stimulate sexual behavior may suppress central arginine vasopressin and V1a receptor activity.

Animals↗
PubMed1996

The role of oxytocin receptors and vasopressin V1a receptors in uterine contractions in rats: implications for tocolytic therapy with oxytocin antagonists.

OBJECTIVE: The objective of the study was to determine in the rat model whether the uterotonic action of vasopressin is mediated by the vasopressin V1a receptor in the uterus, by the oxytocin receptor, or by both. The purpose is to assess whether the anti-V1a activity of oxytocin antagonists is a desirable pharmacologic property in tocolytic therapy for preterm labor. STUDY DESIGN: Dose-response characteristics of the uterotonic action of oxytocin and arginine vasopressin were compared and analyzed by the in vitro cumulative dose-response curve technique. A nonselective oxytocin-V1a receptor antagonist, a selective oxytocin receptor antagonist, and a selective V1a receptor antagonist were selected for this study. Their relative effectiveness in inhibiting the uterine contractile responses induced by oxytocin and by arginine vasopressin in the isolated rat uterus was examined. RESULTS: The uterotonic dose-response curves for oxytocin and arginine vasopressin were parallel and had the same maximal response. The nonselective oxytocin/V1a receptor antagonist and the selective oxytocin receptor antagonist were equally potent in inhibiting the uterine contractions induced by either oxytocin or arginine vasopressin, whereas the selective V1a receptor antagonist had no antiuterotonic activity. Inhibition by the selective oxytocin antagonist caused a similar parallel shift to the right of the dose-response curves for oxytocin and arginine vasopressin. CONCLUSIONS: The parallel dose-response curves for oxytocin and arginine vasopressin suggest that the uterotonic action of vasopressin is also mediated by the oxytocin receptor. Arginine vasopressin binds to both oxytocin and V1a receptors in the uterus, but the activation of V1a receptors appears not to be a mechanism involved in the uterine-stimulating action of vasopressin. The anti-V1a activity of oxytocin antagonists does not contribute to tocolytic efficacy and may represent an undesirable side effect. By blocking the vascular V1a receptors, it may compromise the patient's ability to maintain arterial blood pressure during hemorrhage.

Animals↗
PubMed2000

Impaired potentiation by endothelin-1 and vasopressin of sympathetic contraction in tail artery from hypertensive rats.

OBJECTIVE: To analyse the effects of endothelin-1 and vasopressin on the sympathetic vasoconstriction during hypertension. METHODS: Electrical field stimulation (4 Hz) was applied to isolated, 2 mm segments of the tail artery from spontaneously hypertensive (SHR) and normotensive Wistar-Kyoto (WKY) rats prepared for isometric tension recording. RESULTS: The contraction to electrical stimulation was potentiated by endothelin-1 (10(-10)-10(-8) M) in arteries from WKY but not from SHR, and by vasopressin (10(-12)-10(-10) M) more markedly in arteries from WKY than from SHR. The potentiation by endothelin-1 was reduced more markedly by the antagonist of endothelin ETA receptors BQ-123 (10(-5) M) than by the endothelin ETB receptor antagonist BQ-788 (10(-5) M). The potentiation by vasopressin was reduced by the antagonist of vasopressin V1 receptors d(CH2)5Tyr(Me)AVP (10(-7) M), but not by the vasopressin V2 receptor antagonist d(CH2)5D-Ile2, Ile4AVP (10(-7) M). The blocker of L-type calcium channels verapamil (10(-5) M) reduced the potentiation by both endothelin-1 and vasopressin in arteries from WKY rats, and increased the potentiation by vasopressin in arteries from SHR. Noradrenaline (10(-8)-10(-4) M) contraction was not modified by endothelin-1 (3 x 10(-9) M) or vasopressin (3 x 10(-11) M), and contraction to endothelin-1 (10(-9)-10(-7) M) and vasopressin (10(-10)-10(-7) M) was lower in arteries from SHR than from WKY rats. CONCLUSIONS: (1) The potentiation by endothelin-1 and vasopressin of the sympathetic vasoconstriction, probably due to increased release of noradrenaline, is impaired during hypertension, and (2) this potentiation is mediated mainly by endothelin ETA receptors, and by vasopressin V1 receptors, in both WKY and SHR, and for both peptides it is mediated by L-type calcium channels in arteries from normotensive but not in those from hypertensive animals.

Animals↗
PubMed2000

Vasopressin receptor subtypes on mesenteric and cremasteric arterioles in rat.

We studied the effects of a selective vasopressin V(1A) receptor antagonist [1-(1-(4-(3-acetylaminopropoxy)benzoyl)-4-piperidyl)-3, 4-dihydro-2(1H)-quinolinone (OPC-21268)] and a selective vasopressin V(2) receptor antagonist [5-dimethylamino-1(4-(2-methylbenzoylamino)benzoyl)-2,3,4, 5-tetrahydro-1H-benzazepine (OPC-31260)] on vasopressin-induced contraction of mesenteric and cremasteric arterioles in urethane-anaesthetized rats. Vasopressin was infused intravenously for 60 min or applied topically to arterioles directly. Vasopressin infusion (50, 100 or 500 ng/kg/min) decreased the diameter of both mesenteric and cremasteric arterioles. Vasopressin (500 ng/kg/min)-induced vasoconstriction was antagonized by OPC-21268 (0. 2, 1.0 and 5.0 mg/kg, i.v.), dose-dependently, but not by OPC-31260. Topically applied vasopressin (4.6x10(-10)-4.6x10(-8) M) dose-dependently constricted both microvessels. Pre-administration of OPC-21268 (5.0 mg/kg, i.v.) completely inhibited topically applied vasopressin-induced vasoconstriction in both microvessels, and OPC-31260 partially inhibited it in cremasteric arterioles. These results suggest that vasopressin induces vasoconstriction in rat mesenteric and cremasteric arterioles mainly by stimulating vasopressin V(1A) receptors, while vasoconstriction in cremasteric arterioles is partly associated with stimulation of vasopressin V(2) receptors.

Animals↗
PubMed2002

Involvement of oxytocin and vasopressin in the pathophysiology of preterm labor and primary dysmenorrhea.

Important sources of oxytocin and vasopressin in the human, apart from the supraoptic and paraventricular nuclei of the brain, may be the fetus during labor as well as the endometrium and decidua of the uterus itself. The release of oxytocin and vasopressin to plasma is under influence of ovarian steroids. The two hormones stimulate uterine contractions in pregnant and non-pregnant women via myometrial oxytocin and vasopressin V1a receptors. At the onset of human labor preterm or at term no clear rise in the maternal plasma concentration of oxytocin and/or vasopressin has been demonstrated, but there may be an increased pulse frequency of the release of oxytocin to plasma with the advance of labor. Vasopressin is more potent than oxytocin on isolated myometrium from women undergoing Cesarean section at term. The myometrial concentration of the two receptors is about equal. At the onset of labor preterm and at term there is a tendency to an increase in the density of oxytocin and vasopressin V1a receptors, but there may be a heterogeneous expression of at least the former receptor between different myometrial cells. In advanced labor or after oxytocin treatment the receptors are markedly downregulated. The importance of oxytocin and vasopressin in mechanisms of preterm labor is confirmed by the therapeutic effect in the condition of the oxytocin and vasopressin V1a receptor blocking oxytocin analogue, atosiban. In women with primary dysmenorrhea the plasma concentration of vasopressin is elevated. The in vivo effect of vasopressin on uterine activity in non-pregnant women is about five times more pronounced than that of oxytocin, and it increases premenstrually. Correspondingly, the density of vasopressin V1a and oxytocin receptors vary to the same degree, and a premenstrual rise in the former receptor is seen. Atosiban and the non-peptide compound, SR 49059, which binds to the two receptors in a similar way as atosiban, are therapeutically effective in dysmenorrhea.

Dysmenorrhea↗
PubMed1999

Inhibition of subfornical organ neuronal potassium channels by vasopressin.

The subfornical organ is one of a specialized group of CNS structures devoid of a significant blood-brain barrier, collectively known as the circumventricular organs. While peptides are normally excluded from access to most regions of the CNS, the subfornical organ contains neurons with a high density of receptors for many circulating peptides, including vasopressin. There is a well-established role for the subfornical organ in stimulating the release of vasopressin, and recent evidence suggests that it may also play an important role in mediating the negative feedback actions of vasopressin. The aim of this study was to determine the direct effects of vasopressin on subfornical organ neurons through patch-clamp studies in a dissociated subfornical organ preparation. In current-clamp studies, bath application of 10 nM vasopressin caused depolarizations in 61%, hyperpolarizations in 11%, and no significant change in membrane potential in 28% of neurons tested. We then sought to determine the specific ion channels involved in regulating the vasopressin-induced excitability of subfornical organ neurons through voltage-clamp studies. Vasopressin (10 nM) decreased the peak outward current at +40 mV by 50% (n=7), which was blocked by pretreatment with a V1 receptor antagonist (n=5). Based on these findings, we carried out a systematic characterization of two subformical organ K+ channels, the delayed rectifier (I(K)) and the transient outward current (I(A)). Through voltage isolation of I(K), we found that vasopressin inhibited the steady-state current, by 33+/-7% (n=9). Vasopressin also inhibited the peak I(A) by 27+/-5% (n=8). These data provide the first evidence of a role for K+ channels in mediating the excitatory effects of vasopressin on subfornical organ neurons. The exact physiological roles and sources of vasopressin which may act on subfornical organ neurons are not completely understood at present.

Algorithms↗
PubMed1993

Triphasic response of rat intracerebral arterioles to increasing concentrations of vasopressin in vitro.

To determine how vasopressin affects the vascular tone of the smaller cerebral arterioles, we carried out an in vitro study of isolated and cannulated intracerebral arterioles of rats. We found that increasing concentrations of vasopressin induced a triphasic response of vasodilation (10(-12)-10(-11) M), vasoconstriction (10(-10)-10(-8) M), and vasodilation stabilizing to control diameter (10(-7)-10(-6) M) and that the maximum constriction was twice the maximum dilation in these smaller arterioles [21.2 +/- 13.1% (mean +/- SD) decrease in diameter vs. 11.2 +/- 5.7% increased]. Pretreatment of the arterioles with NG-monomethyl-L-arginine (10(-4) M), a specific inhibitor of endothelium-derived relaxing factor, abolished the vasopressin-induced vasodilation and significantly increased the vasoconstriction. These results suggest that these arterioles were maintained in a dilated state by an endothelium-derived relaxing factor activated by vasopressin. Both vasodilation and vasoconstriction were found to be mediated through vasopressin V1 receptors in a study of arterioles pretreated with d(CH2)5Tyr(Me)arginine vasopressin (10(-6) M), a vasopressin V1 receptor antagonist. These results support the hypothesis that vasopressin may constrict smaller cerebral arterioles while simultaneously dilating larger cerebral arteries. Our results also suggest that vasopressin may aggravate cerebral ischemia in pathological conditions, such as subarachnoid hemorrhage, when the arteriolar response to vasopressin shifts from vasodilation to vasoconstriction due to increased vasopressin levels in plasma and CSF and impaired endothelium-derived relaxation.

Animals↗
PubMed1989

Solubilization of rat liver vasopressin receptors as a complex with a guanine-nucleotide-binding protein and phosphoinositide-specific phospholipase C.

Vasopressin V1 receptors were solubilized from rat liver plasma membranes with the detergent lysophosphatidylcholine. [[3H]Arginine]vasopressin (AVP) binding to the solubilized preparations was specific and saturable, with a dissociation constant of 0.6 nM. Cross-linking of [125I]vasopressin to the solubilized fraction, studied by SDS/polyacrylamide-gel-electrophoretic analysis, demonstrated the presence of a 65 kDa band which was specifically labelled with [125I]vasopressin. Specific binding of [3H]AVP to these solubilized receptors was decreased by guanine nucleotides, but not by adenosine 5'-[beta gamma-imido]triphosphate. Addition of vasopressin increased specific binding of 35S-labelled guanosine 5'-[gamma-thio]triphosphate (GTP[35S]) to the solubilized fractions, indicating co-solubilization of GTP-binding protein(s) [G-protein(s)] and vasopressin receptors. The solubilized fraction was insensitive to both cholera- and pertussistoxin treatment. Immunoblotting of the solubilized fraction with antibodies specific for a phosphoinositide-specific phospholipase C (PI-PLC I) demonstrated the presence of a 60 kDa protein. Anti-PI-PLC I antiserum immunoprecipitated solubilized vasopressin-binding sites from rat liver (V1), but not solubilized vasopressin-binding sites from hog kidney (V2). Similar results were obtained with an anti-PI-PLC I IgG affinity column. The solubilized (V1) receptors were enriched by ion-exchange and high-performance gel-filtration liquid chromatography. Vasopressin-binding activity was co-eluted with PI-PLC I and GTP[S]-binding activity on a DEAE-Sepharose column. The major vasopressin- and GTP[35S]-binding activities were co-eluted with PI-PLC I activity at approx. 240 kDa suggesting that vasopressin receptors from rat liver membranes can be solubilized as a complex of receptor-coupler-effector by using the detergent lysophosphatidycholine.

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