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PubMed2005

Anterior hypothalamic vasopressin modulates the aggression-stimulating effects of adolescent cocaine exposure in Syrian hamsters.

Repeated low-dose cocaine treatment (0.5 mg/kg/day) during adolescence induces offensive aggression in male Syrian hamsters (Mesocricetus auratus). This study examines the hypothesis that adolescent cocaine exposure predisposes hamsters to heightened levels of aggressive behavior by increasing the activity of the anterior hypothalamic-vasopressinergic neural system. In a first experiment, adolescent male hamsters were treated with low-dose cocaine and then scored for offensive aggression in the absence or presence of vasopressin receptor antagonists applied directly to the anterior hypothalamus. Adolescent cocaine-treated hamsters displayed highly escalated offensive aggression that could be reversed by blocking the activity of vasopressin receptors within the anterior hypothalamus. In a second set of experiments, adolescent hamsters were administered low-dose cocaine or vehicle, tested for offensive aggression, and then examined for differences in vasopressin innervation patterns and expression levels in the anterior hypothalamus, as well as the basal- and stimulated-release of vasopressin in this same brain region. Aggressive, adolescent cocaine-treated hamsters showed no differences in vasopressin afferent innervation and/or peptide levels in the anterior hypothalamus compared with non-aggressive, saline-treated littermates. Conversely, significant increases in stimulated, but not basal, vasopressin release were detected from the anterior hypothalamus of aggressive, cocaine-treated animals compared with non-aggressive, saline-treated controls. Together, these data suggest that adolescent cocaine exposure increases aggression by increasing stimulated release of vasopressin in the anterior hypothalamus, providing direct evidence for a causal role of anterior hypothalamic-vasopressin activity in adolescent cocaine-induced offensive aggression. A model for how alterations in anterior hypothalamic-vasopressin neural functioning may facilitate the development of the aggressive phenotype in adolescent-cocaine exposed animals is presented.

Age Factors↗
PubMed2003

Vasopressin: a new target for the treatment of heart failure.

BACKGROUND: Arginine vasopressin is a peptide hormone that modulates a number of processes implicated in the pathogenesis of heart failure. Numerous vasopressin antagonists are currently under development for the treatment of this syndrome. METHODS: Preclinical and clinical data describing the effects of vasopressin and the vasopressin antagonists on both normal physiology and heart failure were reviewed. RESULTS: Through activation of V(1a) and V(2) receptors, vasopressin regulates various physiological processes including body fluid regulation, vascular tone regulation, and cardiovascular contractility. Vasopressin synthesis is significantly and chronically elevated in patients with heart failure despite the volume overload and reductions in plasma osmolality often observed in these patients. Vasopressin also appears to adversely effect hemodynamics and cardiac remodeling, while potentiating the effects of norepinephrine and angiotensin II. The selective V(2) and dual V(1a)/V(2) receptor antagonists tolvaptan and conivaptan, respectively, substantially increase free water excretion and plasma osmolality, reduce body weight, improve symptoms of congestion, and moderately increase serum sodium concentrations in patients with heart failure who present with symptoms of fluid overload. Tolvaptan effectively normalizes serum sodium concentrations in hyponatremic heart failure patients. Conivaptan significantly reduces pulmonary capillary wedge pressure without affecting systemic vascular resistance or cardiac output. The clinical significance of V(1a) receptor antagonism requires further investigation. CONCLUSIONS: Current preclinical and clinical findings with the vasopressin antagonists appear promising, however further evaluation in phase III clinical trials is necessary to define the role of vasopressin antagonism in the treatment of heart failure.

Animals↗
PubMed1996

Intraamniotic deamino(D-Arg8)-vasopressin: prolonged effects on ovine fetal urine flow and swallowing.

OBJECTIVE: Fetal urine is the main source of amniotic fluid, and alterations in urine production have an impact on amniotic fluid dynamics. Intraamniotic arginine vasopressin is absorbed into fetal plasma, but fetal antidiuretic responses may be obscured by vasoconstrictor (V1 receptor) actions of arginine vasopressin. We determined the effects of intraamniotic administration of a specific V2 receptor agonist, deamino(D-Arg8)-vasopressin, on fetal plasma arginine vasopressin immunoreactivity, fetal urine output, and swallowing. STUDY DESIGN: Six chronically prepared pregnant ewes (129 +/- 1 days' gestation) received a single deamino(D-Arg8) (50 micrograms injection into the amniotic fluid with subsequent measurement of fetal plasma arginine vasopressin immunoreactivity, fetal urine flow and osmolality, and fetal swallowing. RESULTS: Within 30 minutes of deamino(D-Arg8)-vasopressin administration, fetal plasma arginine vasopressin immunoreactivity (4.5 +/- 0.5 to 76.4 +/- 21.9 pg/ml) and urine osmolality (135 +/- 13 to 285 +/- 43 mOsm/kg H2O) significantly increased and urine flow decreased (0.18 +/- 0.01 to 0.05 +/- 0.01 ml/kg per minute). After 48 hours urine flow remained reduced (0.08 +/- 0.03 mg/kg per minute) and osmolality remained elevated (399 +/- 18 mOsm/kg H2O). There were no changes in fetal swallowing, systolic (64 +/- 3 mm Hg) or diastolic (42 +/- 3 mm Hg) blood pressure, or heart rate (169 +/- 6 beats/min). CONCLUSIONS: Intraamniotic deamino(D-Arg8)-vasopressin administration evokes persistent fetal antidiuresis in the absence of arginine vasopressin-induced fetal cardiovascular effects or changes in fetal swallowed volume, indicating its suitability as a potential therapeutic agent in amniotic fluid volume disorders such as polyhydramnios.

Amniotic Fluid↗
PubMed2001

Vasopressin induced cyclooxygenase dependent superoxide generation contributes to K(+) channel function impairment after brain injury.

This study determined if vasopressin generates superoxide anion (O2(-)) in a cyclooxygenase dependent manner and if such production contributes to impairment of dilation to activators of ATP sensitive K(+) (K(ATP)) and calcium sensitive K(+) (K(ca)) channels following fluid percussion brain injury (FPI) in newborn pigs equipped with closed cranial windows. Superoxide dismutase (SOD) inhibitable nitroblue tetrazolium (NBT) reduction was determined as an index of O2(-) generation. Under non-brain injury conditions, topical vasopressin (40 pg/ml, the concentration present in CSF following FPI) increased SOD inhibitable NBT reduction from 1+/-1 to 25+/-4 pmol/mm(2). Indomethacin, a cyclooxygenase inhibitor, blunted such NBT reduction (1+/-1 to 5+/-1 pmol/mm(2)), while the vasopressin antagonist, l-(beta-mercapto-beta beta-cyclopentamethylene propionic acid) 2-(o-methyl)-Tyr-AVP (MEAVP) blocked NBT reduction. MEAVP and indomethacin also blunted the NBT reduction observed after FPI. Under non-brain injury conditions, vasopressin (40 pg/ml) coadministered with the K(ATP) and K(ca) channel agonists, cromakalim and NS1619 (10(-8), 10(-6) M) diminished dilation to these K(+) channel agonists while indomethacin partially prevented such impairment (13+/-1 and 23+/-1 vs. 4+/-1 and 10+/-2 vs. 8+/-1 and 19+/-1% for cromakalim in untreated, vasopressin, and vasopressin plus indomethacin treated piglets, respectively). Cromakalim and NS1619 induced pial artery dilation was attenuated following FPI, while indomethacin or MEAVP preadministration partially prevented such impairment (13+/-1 and 23+/-1, sham control; 1+/-1 and 4+/-1, FPI; 8+/-1 and 16+/-3%, FPI-indomethacin pretreated for responses to cromakalim 10(-8), 10(-6) M, respectively). These data show that vasopressin increased O2(-) production in a cyclooxygenase dependent manner and contributed to this production after FPI. These data also show that vasopressin blunted K(ATP) and K(ca) channel mediated cerebrovasodilation in a cyclooxygenase dependent manner. These data suggest that vasopressin induced cyclooxygenase dependent O2(-) generation contributes to K(ATP) and K(ca) channel function impairment after FPI.

Animals↗
PubMed2000

Spatial, cellular and temporal basis of vasopressin potentiation of norepinephrine-induced cAMP formation.

This study investigated the spatial distribution of vasopressin V(1) and beta(1)-adrenoceptors within hippocampal subfields and lamina in an attempt to localize the site(s) of interaction between these two receptor systems. In addition, the cell types, neuronal and glial, in which the vasopressin-induced neuromodulation occurs, were identified. Lastly, the temporal constraints of the potentiation induced by vasopressin were investigated. Results of these analyses demonstrated multiple sites within the hippocampus where the interaction between vasopressin and norephinephrine could occur. Moreover, vasopressin-induced potentiation of adrenergic stimulated cyclase occurred in both hippocampal neurons and glia whereas it did not occur in undifferentiated neurons. Analysis of the temporal constraints of vasopressin-induced potentiation revealed that pre-activation of the vasopressin V(1) receptor for 1 min yielded greater potentiation than simultaneous exposure to vasopressin and norepinephrine. These data provide insights into the spatial and temporal characteristics for the interaction between the vasopressin receptor and adrenoceptor systems and provide a cellular and biochemical rationale for the behavioral findings of Kovács and De Wied.

Adrenergic alpha-Agonists↗
PubMed1998

Stability of the vasopressin V2 receptor-adenylyl cyclase system in rat kidney.

In the Brattleboro rat with diabetes insipidus vasopressin V2 receptor mRNA and the mRNA of various adenylyl cyclase (AC) isoforms are moderately reduced compared with those of normal rats. In the present study renal vasopressin V2 receptor mRNA was modestly higher (by 34%), as was expression of AC 5, 6 and 9 mRNAs (up to 22% greater), in BDI rats treated with the vasopressin V2 receptor agonist desamino-[Arg8] vasopressin than in untreated controls. AC 4 mRNA was decreased by 17% following desamino-[Arg8s] vasopressin treatment. While the stimulatory Gsalpha mRNA was little affected by the desamino-[Arg8] vasopressin treatment, two of the inhibitory G proteins were raised (Galphai-2 by 54% and Galphai-3 by 57%). Treatment of Sprague-Dawley rats with a specific vasopressin V2 receptor antagonist (SR 121463A) was not associated with any marked changes in mRNA expression. These results indicate that the vasopressin V2 receptor adenylyl cyclase system mediating the antidiuretic response to vasopressin is relatively stable. The Gi proteins may be involved in the stabilizing mechanism.

Adenylyl Cyclases↗
PubMed1983

Chronic hypernatremia from a congenital defect in osmoregulation of thirst and vasopressin.

An infant with microcephaly and delayed development was found to have chronic asymptomatic hypernatremia. Computerized brain tomography disclosed dysplasia of the midline structures, septum pellucidum and corpus collosum. Evaluation revealed defective osmoregulation, hypothalamic hypothyroidism, and hypogonadotropinism. He showed no desire to drink at plasma osmolalities over 330 mOsm/kg. His plasma vasopressin levels (less than or equal to 1.4 pg/ml) were inappropriately low relative to his high levels of plasma osmolality (greater than or equal to 310 mOsm/kg), which might be accounted for by either deficient neurohypophyseal vasopressin stores or disturbance of the hypothalamic osmoreceptors governing vasopressin. The first possibility was ruled out by demonstrating normal vasopressin response (167 pg/ml) to nonosmotic (emetic) stimulation. Under baseline conditions, his urine was concentrated up to 747 mOsm/kg and urine volume was low. With water loading, maximal water diuresis developed (urine osmolality 68 mOsm/kg), but his plasma osmolality remained in the hyperosmolar range (312 mOsm/kg). Treatment with a vasopressin analogue, desamino-D-arginine vasopressin, and forced hydration restored plasma osmolality and plasma sodium to normal. These findings indicate a severe defect in the hypothalamic osmoreceptors controlling thirst and vasopressin secretion with normal vasopressin stores and preserved vasopressin responsiveness to nonosmotic stimuli. To our knowledge, this report provides the first documentation of selective osmoreceptor defect in conjunction with congenital dysplasia of midline brain structures.

Brain↗
PubMed2002

Regulation of renal salt and water transporters during vasopressin escape.

Hyponatremia, defined as a serum sodium < 135 mmol/l, is one of the most commonly encountered and serious electrolyte disorders of clinical medicine. The predominant cause of hyponatremia is an inappropriate elevation of circulating vasopressin levels relative to serum osmolality or the 'syndrome of inappropriate antidiuretic hormone secretion' (SIADH). Fortunately, the degree of the hyponatremia is limited by a process that counters the water-retaining action of vasopressin, namely 'vasopressin escape'. Vasopressin escape is characterized by a sudden increase in urine volume with a decrease in urine osmolality independent of circulating vasopressin levels. Until recently, little was known about the molecular mechanisms underlying escape. In the 1980s, we developed an animal model for vasopressin escape in which male Sprague-Dawley rats were infused with dDAVP, a V2-receptor-selective agonist of vasopressin, while being fed a liquid diet. Rats drank a lot of water in order to get the calories they desired. Using this model, we demonstrated that the onset of vasopressin escape (increased urine volume coupled to decreased urine osmolality) coincided temporally with a marked decrease in renal aquaporin-2 (water channel) protein and mRNA expression in renal collecting ducts. This protein reduction was reversible and correlated to decreased water permeability of the collecting duct. Studies examining the mechanisms underlying AQP2 decrease revealed a decrease in V2-receptor mRNA expression and binding, as well as a decrease in cyclic AMP production in response to acute-dDAVP challenge in collecting duct suspensions from these escape animals. Additional studies showed an increase in sodium transporters of the distal tubule. These changes, hypothetically, might help to attenuate the hyponatremia. Future studies are needed to fully elucidate systemic, intra-organ, and cellular signaling responsible for the physiological phenomenon of vasopressin escape.

Animals↗
PubMed1999

[Arg8]-vasopressin-induced increase in intracellular Ca2+ concentration in cultured rat hippocampal neurons.

Changes in intracellular Ca2+ concentration ([Ca2+]i) induced by [Arg8]-vasopressin (AVP) were studied in cultured rat hippocampal neurons by fura-2 fluorometry. AVP (10-1,000 nM) caused a dose-dependent increase in [Ca2+]i. The selective V1 vasopressin receptor agonist [Phe2, Ile3, Orn8]-vasopressin also induced a significant increase in [Ca2+]i, whereas the selective V2 vasopressin receptor agonist [deamino Cys1, D-Arg8]-vasopressin showed no effect. The AVP-induced increase in [Ca2+]i was inhibited by the selective V1 vasopressin receptor antagonist d(CH2)5[Tyr2(Me), Arg8]-vasopressin and nonpeptide V1 antagonist OPC-21268. On the other hand, no antagonistic effects were observed with the V2 vasopressin antagonist desglycinamide-[d(CH2)5, D-Ile2, Ile4, Arg8]-vasopressin and nonpeptide V2 antagonist OPC-31260. The increase in [Ca2+]i induced by AVP was abolished after removal of extracellular Ca2+. In addition, AVP-induced [Ca2+]i elevation was not affected by treatment with verapamil, which blocked the [Ca2+]i increase induced by an isotonic high K(+)-medium (50 mM). However, omega-conotoxin GVIA completely inhibited the effect of AVP. These results suggested that the AVP-induced [Ca2+]i increase in cultured rat hippocampal neurons is due to influx of Ca2+ through V1 VP receptors coupled with N-type calcium channels.

Animals↗
PubMed1981

Phosphatidylinositol metabolism in rat hepatocytes stimulated by vasopressin.

In isolated rat hepatocytes, vasopressin evoked a large increase in the incorporation of [32P]Pi into phosphatidylinositol, accompanied by smaller increases in the incorporation of [1-14C]oleate and [U-14C]glycerol. Incorporation of these precursors into the other major phospholipids was unchanged during vasopressin treatment. Vasopressin also promoted phosphatidylinositol breakdown in hepatocytes. Half-maximum effects on phosphatidylinositol breakdown and on phosphatidylinositol labelling occurred at about 5 nM-vasopressin, a concentration at which approximately half of the hepatic vasopressin receptors are occupied but which is much greater than is needed to produce half-maximal activation of glycogen phosphorylase. Insulin did not change the incorporation of [32P]Pi into the phospholipids of hepatocytes and it had no effect on the response to vasopressin. Although the incorporation of [32P]Pi into hepatocyte lipids was decreased when cells were incubated in a Ca2+-free medium, vasopressin still provoked a substantial stimulation of phosphatidylinositol labelling under these conditions. Studies with the antagonist [1-(beta-mercapto-beta, beta-cyclopentamethylenepropionic acid),8-arginine]vasopressin indicated that the hepatic vasopressin receptors that control phosphatidylinositol metabolism are similar to those that mediate the vasopressor response in vivo. When prelabelled hepatocytes were stimulated for 5 min and then subjected to subcellular fractionation. The decrease in [3H]phosphatidylinositol content in each cell fraction with approximately in proportion to its original phosphatidylinositol content. This may be a consequence of phosphatidylinositol breakdown at a single site, followed by rapid phosphatidylinositol exchange between membranes leading to re-establishment of an equilibrium distribution.

Animals↗
PubMed1982

Effect of acute vasopressin infusion on blood pressure and plasma angiotensin II in normotensive and DOCA-salt hypertensive rats.

1. Arginine vasopressin was infused at 0.5, 2, 6, 18 or 54 ng min(-1) kg(-1) for 1 hr into normal, sham-operated and DOCA-salt hypertensive rats. Complete vasopressin/blood pressure dose-response curves were constructed from circulating plasma vasopressin concentrations measured at the end of each infusion. 2. DOCA-salt hypertensive rats had a higher basal plasma vasopressin concentration (11.1 +/- SD 3.7 fmol/ml) than either the normal (3.9 +/- 2.3, P less than 0.01) or the sham-operated rats (4.5 +/- 2.4, P less than 0.01). 3. The DOCA-salt hypertensive rats did not have my detectable enhancement of pressor sensitivity, compared with either of the two normotensive groups. 4. There was no significant increase in blood pressure in either the normal rats or sham-operated rats until vasopressin was infused at 2 ng min(-1) kg(1), when the plasma concentration was between 30 and 40 fmol/ml. 5. Subpressor infusion of vasopressin in the normal and sham-operated rats, which gave plasma concentrations of 22-23 fmol/ml, completely suppressed plasma angiotensin II to levels similar to the basal values found in the DOCA- salt hypertensive rats (10.5 +/- 2.3, 14.5 +/- 4.5 and 8.0 +/- 1.6 fmol/ml respectively). 6. These findings suggest that the mechanism of vasopressin involvement in DOCA-salt hypertension is as yet unclear, that short-term changes in vasopressin concentration appear unimportant in the regulation of normal blood pressure, that small physiological changes of vasopressin in normal rats may be important in the regulation of renin secretion, and that the increase in vasopressin concentration seen in DOCA-salt hypertension may contribute to the suppression of renin and angiotensin II in this state.

Angiotensin II↗
PubMed2003

The effects of neonatal castration on the subsequent behavioural response to centrally administered arginine vasopressin and the expression of V1a receptors in adult male prairie voles.

Centrally administered arginine vasopressin induces the formation of partner preferences in male prairie voles (Microtus ochrogaster). The expression of many vasopressin-regulated behaviours is testosterone dependent. In this study, we tested the hypothesis that early exposure to gonadal steroids are necessary to establish the typical response of adult male prairie voles to exogenous vasopressin, predicting that adult males which were castrated neonatally would not form partner preferences in response to centrally administered vasopressin. We also examined the effect of neonatal castration on the expression of vasopressin (V1a) receptors. Voles were castrated on the day of birth (NEOCAST), sham-castrated on the day of birth (NEOSHAM) or castrated as adults (ADULTCAST). With the exception of one group of neonatal sham males (NEOSHAM CON), which served as a control for the effects of vasopressin, as adults, all males received a 1- micro l intracerebroventricular injection of vasopressin (100 ng) in artificial cerebrospinal fluid. In addition, 2 weeks before testing, one group of neonatally castrated males received an implant of testosterone propionate (NEOCAST + TP). Between 60 and 90 days of age, an internal cannula was placed in the lateral cerebral ventricle and, 24 h later, males were injected with vasopressin. Subsequently, after an additional 15 min, males were cohabitated with a female 'partner' for 1 h. Immediately following cohabitation, males were placed in a Y-shaped partner preference test apparatus for 3 h, in which the male had access to the 'partner' and a novel female, 'stranger.' Time spent with the partner versus the stranger was compared within and between treatments. The results were found to support our hypothesis as the NEOSHAM and ADULTCAST males formed partner preferences, spending more time with the partner, and they spent significantly more time with their partner than did NEOSHAM CON, NEOCAST or NEOCAST + TP males. Replacement of testosterone in neonatally castrated males did not restore partner preference formation in response to vasopressin in adult males. Finally, neonatal castration did not affect the distribution of V1a receptors.

Age Factors↗
PubMed1989

Heterologous desensitization of bombesin-induced mitogenesis by prolonged exposure to vasopressin: a post-receptor signal transduction block.

Prolonged exposure of quiescent Swiss 3T3 cells to vasopressin prevents mitogenic stimulation on subsequent addition of bombesin. This heterologous desensitization is selective and can be mimicked by vasopressin agonists, including [Lys8]vasopressin and oxytocin but not by the V1-type-specific vasopressin receptor antagonist [Pmp1,O-Me-Tyr2,Arg8]vasopressin [where Pmp is 1-(beta-mercapto-beta,beta-cyclopenthamethylene propionic acid)]. Furthermore, vasopressin-induced loss of responsiveness to bombesin can be blocked by addition of this antagonist, indicating that heterologous desensitization is mediated through the vasopressin receptor. Desensitization requires prolonged incubation (half-maximal desensitization occurring after approximately 20 hr of pretreatment) and continuous protein synthesis. Bombesin responsiveness is restored by incubation in the absence of vasopressin. Pretreatment does not alter the number, affinity, or internalization capacity of the bombesin receptors. However, the induction of the protooncogene c-fos by bombesin is profoundly inhibited after vasopressin pretreatment. We suggest that the coupling of the activated bombesin receptor to the generation of its early signals is impaired in desensitized cells.

Animals↗
PubMed2004

Degradation of wild-type vasopressin precursor and pathogenic mutants by the proteasome.

Mutations in the gene encoding the antidiuretic hormone arginine vasopressin cause autosomal dominant neurogenic diabetes insipidus. Autoptic data in affected individuals suggest that the neurons expressing mutant vasopressin undergo selective degeneration. Expression studies have shown that the mutants are retained in the endoplasmic reticulum, but how this trafficking defect is linked to neurotoxicity is unknown. One possibility is that unsecreted mutant precursors, or degradation products thereof, are cytotoxic. We therefore investigated the fate of endoplasmic reticulum-retained pathogenic mutants. Our data show that the mutants are retrotranslocated to the cytosol and degraded by the proteasome. In the presence of proteasomal inhibitors, three distinct un- or deglycosylated cytosolic species of vasopressin precursors were stabilized: pre-pro-vasopressin, pro-vasopressin, and an N-terminally truncated form. In addition to the retrotranslocated forms, a fraction of the newly synthesized precursor was not translocated, but was synthesized into the cytosol due to inefficient function of the vasopressin signal peptide. As a result, cytosolic pre-pro-vasopressin and its degradation product were also recovered when wild-type vasopressin was expressed. Cytosolic forms of vasopressin might trigger cytotoxicity in vivo, as has been proposed in the case of prion protein, which also contains an inefficient N-terminal signal peptide.

Amino Acid Sequence↗
PubMed1999

Effect of propofol on arachidonate cascade by vasopressin in aortic smooth muscle cells: inhibition of PGI2 synthesis.

BACKGROUND: The mechanisms underlying the vascular effects of propofol are not fully understood. Vasopressin, a potent vasoactive peptide, stimulates the arachidonate cascade and the synthesis of prostacyclin (PGI2; the main metabolite of the cascade in vascular smooth muscle cells). Arachidonic acid (AA) release by phospholipases is the rate-limiting step in the cascade. We investigated the mechanisms underlying vasopressin-induced AA release and the effect of propofol on PGI2 synthesis in a rat aortic smooth muscle cell line: A10 cells. METHODS: In cultured A10 cells pretreated with propofol, the stimulation by vasopressin of AA release and PGI2 synthesis was evaluated by measuring [3H]AA and 6-keto PGF1alpha, respectively, in the culture medium. The effects of propofol on vasopressin-induced activation of phosphoinositide-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing phospholipase D were evaluated by measuring inositol phosphate formation and choline formation, respectively. RESULTS: A phospholipase C inhibitor and a phosphatidic acid phosphohydrolase inhibitor both attenuated vasopressin-induced AA release and PGI2 synthesis, as did a phospholipase A2 inhibitor. Propofol inhibited vasopressin-induced activation of phosphoinositide-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing phospholipase D, but this effect of propofol was significant only at supraclinical concentration (0.1 mM). Propofol reduced vasopressin-induced PGI2 synthesis. The inhibitory effect was observed at concentrations (10 microM-0.1 mM) higher than those used clinically. CONCLUSIONS: Propofol suppresses the arachidonate cascade caused by vasopressin at least partly by inhibiting phosphoinositide-hydrolyzing phospholipase C and phosphatidylcholine-hydrolyzing phospholipase D, resulting in the inhibition of PGI2 synthesis. Propofol-mediated inhibition of vasopressin-stimulated synthesis of PGI2 may reduce the vasorelaxation by propofol.

Anesthetics, Intravenous↗
PubMed1986

Role of central vasopressin in cardiovascular regulation.

Using techniques of intracerebroventricular administration of vasopressin, microinjection of vasopressin into specific brain nuclei, electrical stimulation, and ablation of specific nuclei, we found that vasopressin, through an effect on central neural structures, increases mean arterial pressure and heart rate via an increase in sympathetic outflow and that deoxycorticosterone acetate (DOCA)-salt hypertensive rats show increased sensitivity and responsiveness to the central effects of vasopressin. Furthermore, we found that an important central target area for the cardiovascular effects of vasopressin is the pontine nucleus locus coeruleus. Ablation of the locus coeruleus markedly attenuates the cardiovascular effects of vasopressin as well as the development of DOCA-salt hypertension. Taken together, our results suggest a link between vasopressin, the locus coeruleus, and the sympathetic nervous system in normal cardiovascular regulation as well as in the pathogenesis of DOCA-salt hypertension. Our studies support the hypothesis that vasopressin modifies sympathetic drive through an action on central neural target areas, such as the locus coeruleus controlling sympathetic outflow. Our data further suggests that vasopressin may participate in the pathogenesis of DOCA-salt hypertension by inducing stimulation of the sympathetic nervous system at the region of the locus coeruleus in this model.

Animals↗
PubMed1988

The vasopressin precursor in the Brattleboro (di/di) rat.

The vasopressin precursor in the rat hypothalamus has been studied, using trypsin to release desglycinamide vasopressin and coupling it to glycinamide (T & G treatment). The resulting amidated nonapeptide was detected and measured with a radioimmunoassay for vasopressin. The "vasopressin" produced in this way had the full immunoreactivity of the authentic peptide but eluted from an hplc column 1 min earlier and appeared to have a larger molecular weight. It was found that T&G treatment generated vasopressin immunoreactivity in extracts of the supraoptic nucleus (SON) of the Brattleboro rat in just the same way as it did in normal animals. Furthermore, this procedure produced vasopressin immunoreactivity in those hplc fractions from Brattleboro SON extracts that corresponded with the elution time of vasopressin precursor. Similar amounts of "vasopressin" could be generated from Brattleboro and normal SONs. These results support the suggestion that the Brattleboro SON synthesizes an aberrant vasopressin precursor which is not processed by the cell.

Animals↗
PubMed1992

Vasopressin-stimulated [3H]-inositol phosphate and [3H]-phosphatidylbutanol accumulation in A10 vascular smooth muscle cells.

1. The characteristics of vasopressin-stimulated phosphatidylinositol 4,5 bisphosphate (PtdIns(4,5)P2) and phosphatidylcholine (PtdCh) hydrolysis were examined in A10 vascular smooth muscle cells (VSMC), by assessing the formation of [3H]-inositol phosphates ([3H]-IP) and the accumulation of the phospholipase D (PLD) specific product, [3H]-phosphatidylbutanol ([3H]-PtdBuOH). 2. Vasopressin ([Arg8]-VP) and a number of related analogues stimulated the accumulation of [3H]-IP and [3H]-PtdBuOH with similar EC50 values, generating the same rank order of potency for each response (Arg8-VP = vasotocin = Lys8-VP much greater than oxytocin). 3. Inhibition of vasopressin-stimulated [3H]-IP and [3H]-PtdBuOH accumulation by the V1a receptor antagonists, Des-Gly9[beta-mercapto-beta,beta,-cyclopentamethylene propionyl, O-Et-Tyr2,Val4,Arg8]-vasopressin generated similar IC50 values suggesting that both these responses are mediated through the activation of a single V1a receptor subtype. 4. The onset of vasopressin-stimulated inositol-1,4,5-trisphosphate (Ins(1,4,5)P3) mass formation preceded [3H]-PtdBuOH accumulation indicating that PtdCh hydrolysis was activated subsequent to PtdIns(4,5)P2 breakdown. 5. The protein kinase C (PKC) activator, tetradecanoylphorbol acetate (TPA) also stimulated [3H]-PtdBuOH accumulation. Preincubation with the PKC inhibitor Ro-31-8220 abolished both TPA- and vasopressin-stimulated [3H]-PtdBuOH, suggesting that the intermediate activation of protein kinase C is involved in the regulation of PLD by vasopressin. 6. Pretreatment of the A10 VSMC with Ro-31-8220 (100 microM) also potentiated vasopressin-stimulated Ins(1,4,5)P3 mass formation.Therefore stimulation of PKC may have opposing roles in the regulation of agonist activation of PLC and PLD.7. Preincubation of the cells with EGTA, verapamil, or the receptor-operated calcium channel antagonist, SK&F 96365, reduced vasopressin-stimulated [3H]-PtdBuOH accumulation by approximately 30%, suggesting that influx of calcium has a significant role to play in the regulation of vasopressinstimulated PLD activity.

Animals↗