Higher Arginine Vasopressin Concentrations Research Articles

Serial plasma vasopressin concentration in healthy and hospitalised neonatal foals

Vasopressin dysregulation occurs in critically ill human patients and in neonatal foals. Limited data about serial plasma vasopressin dynamics exist in sick neonatal foals. To evaluate serial plasma arginine vasopressin (AVP) concentrations in sick neonatal foals. Prospective, longitudinal clinical study. Plasma samples were collected from 7 healthy and 26 sick foals before and after initial fluid resuscitation and 12, 24, 36, 48 and 96 h after presentation. Foals with a modified sepsis score ≥ 11 were considered septic. Admission AVP was increased in septic foals compared to healthy and to sick, nonseptic foals. There were no significant differences between groups on subsequent days. Nonsurvivors had higher AVP concentrations than survivors. Plasma AVP concentrations are higher in septic foals on admission than in healthy and sick nonseptic foals. Higher early plasma AVP concentrations are associated with increased mortality.

The role of arginine vasopressin in diabetes-associated increase in glucagon secretion

The purpose of this study was to investigate the role of arginine vasopressin (AVP) on glucagon secretion in both normal and diabetic rats. Diabetes was induced by intravenous administration of 50 mg/kg streptozotocin, 14 days before pancreatic perfusion. Diabetic rats were maintained on insulin replacement therapy until ∼48 h before the perfusion experiments. Both glucagon and AVP were determined in the effluent of the perfused pancreas using RIA. Both normal and diabetic rats had similar basal glucagon secretion. AVP (3–30 pM) increased glucagon secretion from both normal and diabetic rats in a concentration-dependent manner. However, diabetic subjects were more sensitive to AVP administration than normal subjects with regard to glucagon secretion. By comparison of the areas under the curves, AVP-induced glucagon secretion in diabetic rats was ∼2-fold that of the normal rats. In addition, immunoreactive AVP was detected in the effluent of the perfused pancreas, and diabetic rats had 70% higher AVP concentrations in the pancreatic effluent than normal rats. We conclude that AVP is secreted from the pancreas and diabetic rats can secrete more AVP from the pancreas than normal rats. Consequently, AVP may have a greater impact on glucagon secretion in diabetic subjects than normal ones. AVP might play an important role in the hypersecretion of glucagon in diabetic subjects.

Effects of angiotensin II, arginine vasopressin and tromboxane A2 in renal vascular bed: role of rho-kinase.

Angiotensin II (Ang II), arginine vasopressin (AVP) and tromboxane A(2) (TxA(2)) are dissimilar vasoconstrictors involved in regulating renal circulation. Whereas Ang II is primarily a physiological modulator, AVP and TxA(2) play important roles under pathological conditions. Previously, we have shown variable importance of intracellular Ca(2+) and protein kinase C for their mode of action (Ang II > AVP >U-46619), but the cell signalling via rho-associated kinase (ROK) is a common pathway. The aim of this study was to determine their sites of action in the renal vascular bed and the corresponding role of ROK at the microvascular level. Glomerular blood flow (GBF) and luminal diameter of different vessels (10-70 micro m) were measured in the split hydronephrotic kidney of anaesthetized rats. The tissue bath concentration of Ang II, AVP or the TxA(2) agonist U-46619 was adjusted to reduce GBF by approximately 50%. The measurements were repeated after adding a sub-maximal dose of the ROK inhibitor Y-27632 into the bath. Ang II constricted all vessels significantly, the constriction being least in the proximal segment of the arcuate artery ( approximately 70 micro m). Significant constrictions due to AVP were found only in interlobular and arcuate arteries (20-70 micro m), but not in the afferent and efferent arterioles. U-46619 constricted only the arcuate artery (> or = 50 micro m). Y-27632 (10(-4) M) dilated all vessels significantly and increased GBF by 65%. Thereafter, effects of all agonists were severely attenuated. Control reductions in GBF could be obtained at higher concentrations of AVP (10-fold) and U-46619 (5-fold) and a lesser GBF reduction with Ang II (100-fold) without changes in the respective patterns of vascular constriction. Our data indicate that the agonists, in the order Ang II, AVP and TxA(2), constrict larger vessels within the renal vascular tree via activation of ROK. Therefore, ROK inhibitors may provide a therapeutic tool to antagonize pathological vasospasm of conduit vessels, which are resistant to other vasodilators.

Enhanced cardiac contractility after gene transfer of V2 vasopressin receptors In vivo by ultrasound-guided injection or transcoronary delivery.

Systemic levels of arginine vasopressin (AVP) are increased in congestive heart failure, resulting in vasoconstriction and reduced cardiac contractility via V(1) vasopressin receptors. V(2) vasopressin receptors (V2Rs), which promote activation of adenylyl cyclase, are physiologically expressed only in the kidney and are absent in the myocardium. Heterologous expression of V2Rs in the myocardium could result in a positive inotropic effect by using the endogenous high concentrations of AVP in heart failure. We tested gene transfer with a recombinant adenovirus for the human V2R (Ad-V2R) to stimulate contractility of rat or rabbit myocardium in vivo. Ultrasound-guided direct injection or transcoronary delivery of adenovirus in vivo resulted in recombinant receptor expression in the myocardial target area, leading to a substantial increase in [(3)H]AVP binding. In 50% of the cardiomyocytes isolated from the directly injected area, single-cell shortening measurements detected a significant increase in contraction amplitude after exposure to AVP or the V2R-specific desmopressin (DDAVP). Echocardiography of the target myocardial area documented a marked increase in local fractional shortening after systemic administration of DDAVP in V2R-expressing animals but not in control virus-treated hearts. Simultaneous measurement of global contractility (dP/dt(max)) confirmed a positive inotropic effect of DDAVP on left ventricular function in the Ad-V2R-injected animals. Adenoviral gene transfer of the V2R into the myocardium increases cardiac contractility in vivo. Heterologous expression of cAMP-forming receptors in the myocardium could lead to novel strategies in the therapy of congestive heart failure by bypassing the desensitized beta-adrenergic receptor-signaling cascade.

Adenoviral gene transfer of the human V2 vasopressin receptor improves contractile force of rat cardiomyocytes.

In congestive heart failure, high systemic levels of the hormone arginine vasopressin (AVP) result in vasoconstriction and reduced cardiac contractility. These effects are mediated by the V1 vasopressin receptor (V1R) coupled to phospholipase C beta-isoforms. The V2 vasopressin receptor (V2R), which promotes activation of the Gs/adenylyl cyclase system, is physiologically expressed in the kidney but not in the myocardium. Expression of a recombinant V2R (rV2R) in the myocardium could result in a positive inotropic effect via the endogenous high concentrations of AVP in heart failure. A recombinant adenovirus encoding the human V2R (Ad-V2R) was tested for its ability to modulate the cardiac Gs/adenylyl cyclase system and to potentiate contractile force in rat ventricular cardiomyocytes and in H9c2 cardiomyoblasts. Ad-V2R infection resulted in a virus concentration-dependent expression of the transgene and led to a marked increase in cAMP formation in rV2R-expressing cardiomyocytes after exposure to AVP. Single-cell shortening measurements showed a significant agonist-induced contraction amplitude enhancement, which was blocked by the V2R antagonist, SR 121463A. Pretreatment of Ad-V2R-infected cardiomyocytes with AVP led to desensitization of the rV2R after short-term agonist exposure but did not lead to further loss of receptor function or density after long-term agonist incubation, thus demonstrating resistance of the rV2R to downregulation. Adenoviral gene transfer of the V2R in cardiomyocytes can modulate the endogenous adenylyl cyclase-signal transduction cascade and can potentiate contraction amplitude in cardiomyocytes. Heterologous expression of cAMP-forming receptors in the myocardium could lead to novel strategies in congestive heart failure by bypassing the desensitized beta-adrenergic receptor signaling.

AVPR2 variants and V2 vasopressin receptor function in nephrogenic diabetes insipidus

The AVPR2 gene encodes the type 2 vasopressin receptor, a member of the vasopressin/oxytocin receptor subfamily of G protein-coupled receptors. Disruption of AVPR2 causes X-linked congenital nephrogenic diabetes insipidus (NDI), yet the functional significance of most gene sequence variations found in association with NDI has not been proven. The large number of naturally occurring AVPR2 mutations constitutes a model system for studying the structure-function relationship of G protein-coupled receptors. This analysis can be aided by examining amino acid sequence variation and conservation among evolutionarily disparate members of the subfamily. Twenty-five new NDI patients were evaluated by DNA sequencing for mutations in AVPR2. Receptors encoded by eighteen NDI alleles were tested for physiologic signaling activity in response to varying concentrations of arginine vasopressin (AVP) in a sensitive cell culture assay. Seventeen amino acid sequences from the vasopressin/oxytocin receptor subfamily were aligned and conserved residues were identified and correlated with the locations of NDI associated variations. Twenty-four variant alleles were found among the 25 new patients. Thirteen had no prior family history of expressed NDI. All 18 of the NDI-associated AVPR2 alleles tested for function demonstrated diminished response to stimulation with AVP. Twelve failed to respond at all, whereas six signaled only at high AVP concentrations. Evolutionarily conserved residues clustered in the transmembrane domains and in the first and second extracellular loops, and NDI-associated missense mutations appeared mostly in the conserved domains. Sporadic cases are frequent and they usually represent the X-linked rather than the autosomal form of NDI. Genetic and functional testing can confirm this in individual cases. Mutations in this study affecting ligand binding domains tend to retain partial signaling in vitro, whereas those that introduce a charged residue in a transmembrane domain are inactive. The minimal partial signaling observed in cultured cells is unlikely to correlate with clinically significant urine concentrating ability. Other AVPR2 mutations with milder effects on receptor function probably exist, but may not be expressed clinically as typical NDI.

Mechanism of lithium-induced polyuria in the rat

While many studies have demonstrated a nephrogenic diabetes insipidus syndrome (NDI) with prolonged lithium (Li) treatment, experiments in the isolated rat papillary collecting duct have suggested that the defect may be due to a circulating factor that inhibits the action of arginine vasopressin (AVP). Since Li-treatment can produce a form of hyperparathyroidism and parathyroid hormone (PTH) can act as a partial agonist to AVP, in vivo and in vitro studies were performed on rats made polyuric by daily intraperitoneal (i.p.) Li (4 mmol/kg) treatment. Li-treatment for three weeks produced an increase in PTH (194 +/- 20 compared with 118 +/- 18 pg/ml in control rats; P < 0.01) as well as an increase in the plasma calcium concentration (2.38 +/- 0.05 compared with 2.25 +/- 0.04 mmol/liter; P < 0.05). Clearance studies were performed on water loaded Li-treated and control rats, and the defect in urine concentration was only observed with a low physiological concentration of AVP (10 mU/kg body wt over 5 min). Maximal urine osmolality was 328 +/- 31 compared with 613 +/- 81 mOsm/kg (P < 0.05) in controls. There was no detectable difference with a prolonged maximal physiological AVP concentration (10 mU bolus and 50 mU/kg body wt per hr) and papillary solute concentrations were unchanged. When Li-treated rats had been parathyroidectomized (PTX), a significant difference in urine concentration with the low AVP concentration could not be demonstrated when compared to non-PTX control rats. In the isolated papillary collecting duct preparation a medium was used that contained fresh plasma from Li-treated or control rats, both intact and PTX. Experiments using plasma from Li-treated intact rats produced only a 25.4 +/- 5.1% increase in diffusional water permeability with the addition of AVP (200 microU/ml) compared to 52.6 +/- 9.0% in control rats (P < 0.01). However, when plasma from Li-treated PTX rats was used, the AVP induced increase in water permeability (54.7 +/- 11.2%) was not significantly different from that observed in PTX control rats. These studies show that the NDI-like defect in Li-treatment is small and easily overcome by higher concentrations of AVP and suggests that the concentration defect is at least in part due to increased circulating levels of PTH acting as a partial agonist to AVP and thereby inhibiting its hydroosmotic action.

Vasopressin induces frequency-modulated repetitive calcium transients in single insulin-secreting hit cells

Ca 2+ is central to the stimulation of insulin secretion from pancreatic β-cells. Arginine-vasopressin (AVP) may participate in the modulation of insulin release. In the present study, the AVP-induced changes in cytosolic free Ca 2+ ([Ca 2+] i) were investigated in single fura-2 loaded insulin-secreting HIT cells. Stimulation with AVP (0.1–5 nM) caused repetitive Ca 2+ transients. The frequency but not the amplitude of the Ca 2+ transients was modulated by the concentration of AVP. High concentrations of AVP (10–100 nM) triggered a biphasic rise in [Ca 2+] i. In Ca 2+-free medium AVP caused only one or two Ca 2+ transients. Withdrawal of extracellular Ca 2+ rapidly abolished the AVP-induced Ca 2+ transients in all cells tested. The Ca 2+ channel blocker, verapamil (50 μM), reduced amplitude and frequency of the Ca 2+ transients by about 25% and 60%, respectively, and terminated the Ca 2+ transients in 2 of 6 cells. When HIT cells were incubated in Ca 2+-free medium, and extracellular Ca 2+ was restored, there was a small increase in [Ca 2+] i. If, however, the agonist-sensitive Ca 2+ pool was functionally depleted by repetitive stimulation with high concentrations of AVP or thapsigargin in Ca 2+-free medium before extracellular Ca 2+ was restored, an agonist-independent increase in [Ca 2+] i was observed, which was transiently larger than in the control cells, and was mainly preserved in the presence of verapamil. Thus, depletion of the agonistsensitive Ca 2+ pool enhances the influx of extracellular Ca 2+ through a Ca 2+ entry mechanism independent from verapamil-sensitive voltage-dependent Ca 2+ channels (VDCC). In conclusion, the AVP-induced Ca 2+ response in single HIT cells is periodic in nature with frequency-modulated repetitive Ca 2+ transients. AVP mobilizes Ca 2+ from intracellular pools, but influx of extracellular Ca 2+ partly through verapamil-sensitive VDCC, and partly through an additional, VDCC-independent pathway, which could be controlled by the filling state of the agonist-sensitive Ca 2+ pool, is required for maintaining the repetitive nature of the Ca 2+ response.

Effects of testosterone on the behavioral response to arginine vasopressin microinjected into the central gray and septum

Arginine vasopressin (AVP) plays an important role in the control of a gonadal hormone-dependent communicative behavior in the Syrian hamster ( Mesocricetus auratus) called flank marking. Previous studies have shown that gonadal hormones alter the amount of flank marking stimulated by the microinjection of AVP into the medial preoptic area-anterior hypothalamus (MPOA-AH). The purpose of the present study was to determine if testicular hormones alter the amount of flank marking stimulated by the microinjection of AVP into two other sites involved in the control of flank marking, the lateral septum-bed nucleus of the stria terminalis (LS-BNST) and the central gray. The data of the present study indicate that testicular hormones may influence the amount of AVP-stimulated marking in the central gray and LS-BNST; however, these effects are subtle and appear to occur primarily at high concentrations of AVP. When taken together with previous studies, these data indicate that gonadal hormones have greater effects on AVP-stimulated marking in the MPOA-AH than in the LS-BNST or central gray.

Multiple cytosolic calcium signals and membrane electrical events evoked in single arginine vasopressin-stimulated corticotrophs.

The action of arginine vasopressin (AVP) on cytosolic free Ca2+ concentration ([Ca2+]i) was investigated in single rat pituitary corticotrophs using indo-1 microfluorimetry, in part in combination with the monitoring of membrane electrical events with the perforated patch-clamp technique. In corticotrophs showing the series of short-lived [Ca2+]i rises (transient pattern) in response to corticotropin-releasing factor, 100 nM AVP evoked either the transient pattern or a [Ca2+]i spike followed by a sustained plateau (spike/plateau pattern). Not all corticotrophs responded to changes in AVP concentration in the same manner. Some cells exhibited a concentration-dependent increase in [Ca2+]i transient activity, whereas others showing the spike/plateau at high AVP concentrations responded to low agonist concentrations by two [Ca2+]i responses: a slow rising step or two to three sinusoidal-like oscillations. Combined [Ca2+]i and patch-clamp recordings as well as manipulation of extracellular Ca2+ showed that both transient pattern and the plateau of spike/plateau response depended on Ca2+ entry mainly through voltage-gated, dihydropyridine-sensitive Ca2+ channels. By contrast, step, oscillations, and spike were due to Ca2+ release from internal stores. These Ca(2+)-mobilizing responses caused the activation of Ca(2+)-activated, apamin-sensitive K+ channels, which led to a membrane hyperpolarization. These results reveal cell-specific [Ca2+]i signals and associated electrical events in individual AVP-stimulated corticotrophs.

Fluid balance in elderly patients following acute stroke.

We studied the relationship between plasma osmolality, arginine vasopressin (AVP), and fluid input in patients during the acute phase of a first stroke. Fifteen consecutive patients were studied (median age 79) and their blood sampled on days 0, 1, 2, 3, 7 and 14. Plasma osmolality was related to fluid input over days 0-3 (p = 0.0013) and AVP over 14 days (p less than 0.001). Patients with a poor outcome had higher AVP concentrations (p = 0.02). Those on intravenous fluids received a higher volume (p less than 0.01) and had a lower plasma osmolality (p = 0.04). The results of this preliminary study indicate that a standard regime for fluid input is inappropriate.

CALCIUM-CHANNEL BLOCKING AGENTS VERAPAMIL AND DILTIAZEM ARE INHIBITORS OF VASOPRESSIN-INDUCED HUMAN PLATELET ACTIVATION

1. This study investigated the influences of calcium-channel blocking agents verapamil and diltiazem on platelet responses induced by arginine vasopressin (AVP) and lysine vasopressin (LVP). 2. The substances inhibited platelet aggregation induced by both low and high AVP concentrations, LVP and adrenaline plus AVP. IC50 values of each drug are lower than those determined for ADP- and collagen-elicited aggregation. Verapamil and diltiazem also decreased AVP-induced thromboxane B2 synthesis. 3. Other series of experiments showed that the addition of ethyleneglycol-bis-(beta-amino-ethyl ether) N, N'-tetra-acetic acid to platelet-rich plasma samples also prevented the platelet response to vasopressin polypeptides. 4. Our data provide evidence that the effects of verapamil and diltiazem on vasopressin-induced platelet responses may be directly related to inhibition of extracellular calcium entry.

AVP stimulates adenylyl cyclase and phospholipase C in reciprocal fashion in cultured RIMCT cells

In cultured rat inner medullary collecting tubule (RIMCT) cells, arginine vasopressin (AVP) stimulates adenylyl cyclase (AC) activity in dose-dependent fashion, with no response at concentrations of 10(-10) M or below and with peak activity at 10(-7) M AVP. In contrast, AVP-stimulated phospholipase (PLC) activity is greatest at concentrations at which there is no effect on AC and decreases at higher concentrations of AVP, becoming undetectable at 10(-7) M. Increasing cellular adenosine 3',5'-cyclic monophosphate (cAMP) content with either exogenous ClPheScAMP or forskolin eliminates inositol trisphosphate production in response to 10(-13) M AVP. Conversely, inhibition of AC by 2',5'-dideoxyadenosine (DDA) unmasks PLC activity in response to 10(-7) M AVP that is not observed in the absence of DDA. Similarly, DDA prevents inhibition of epidermal growth factor-stimulated PLC by AVP. These findings demonstrate the reciprocal relationship between AVP-stimulated AC and PLC activities in cultured RIMCT cells, which may explain previous divergent results regarding the ability of AVP to stimulate PLC in this tissue.

Dose-dependent heterogenous actions of vasopressin in rabbit cortical collecting ducts.

In cortical collecting ducts (CCD), arginine vasopressin (AVP) has been proposed to autoinhibit its own hydrosmotic effect through stimulation of prostaglandin (PG) synthesis or binding to a receptor coupled to phosphatidylinositol (PI) hydrolysis, the so-called V1-receptor, with resultant elevation of intracellular Ca2+ concentration [( Ca2+]i) and activation of protein kinase C (PKC). Using isolated perfused rabbit CCD, we examined whether blocking the negative feedback by a PKC inhibitor, staurosporine (SSP), or a cyclooxygenase inhibitor, indomethacin (IND), enhances AVP-induced increase in hydraulic conductivity (Lp). The Lp induced by a pharmacological concentration (23 nM) of AVP was lower than that induced by 230 pM AVP. This blunted Lp response to 23 nM AVP was significantly restored by SSP or IND pretreatment. In contrast, both SSP and IND did not affect the Lp induced by 23 pM or 230 pM AVP. Fluorescence microscopy of isolated perfused CCD using fura-2 showed a spike-like increase in [Ca2+]i only by 23 nM but not by 23 or 230 pM AVP. We conclude that 1) AVP can increase [Ca2+]i, activate PKC, and stimulate PG synthesis in CCD with resultant autoregulation of its own hydrosmotic effect and 2) importantly, however, this negative feedback occurs only with pharmacologically high concentrations of AVP. Therefore it is unlikely that circulating AVP, via binding to receptors on CCD, autoregulates water transport through activating PG synthesis and/or PI breakdown.

Neuroendocrine activation after acute myocardial infarction.

The extent of neuroendocrine activation, its time course, and relation to left ventricular dysfunction and arrhythmias were investigated in 78 consecutive patients with suspected acute myocardial infarction. High concentrations of arginine vasopressin were found within six hours of symptoms, even in the absence of myocardial infarction (n = 18). Plasma catecholamine concentrations also were highest on admission, whereas renin and angiotensin II concentrations rose progressively over the first three days, not only in those with heart failure but also in patients with no clinical complications. Heart failure, ventricular tachycardia, and deaths were associated with extensive myocardial infarction, low left ventricular ejection fraction, and persistently high concentrations of catecholamines, renin, and angiotensin II up to 10 days after admission, whereas in uncomplicated cases concentrations had already returned to normal.

Arginine Vasopressin in Amniotic Fluid, Arterial and Venous Cord Plasma and Maternal Venous Plasma

High concentrations of arginine vasopressin (AVP) in arterial umbilical cord blood at the time of delivery have been attributed to either a generalized increase in the activity of the fetal endocrine system at the onset of labor or to fetal asphyxia. We measured AVP in amniotic fluid, arterial and venous cord blood and in maternal venous blood from 13 patients at 38-40 weeks of gestation at the time of elective cesarean section with a nonasphyxic fetus (group I), in amniotic fluid from 19 patients at 15-17 weeks of gestation (group II) and in venous blood from 13 nonpregnant control subjects (group III). Our results showed a high concentration of AVP in the amniotic fluid both in the middle and at the end of normal pregnancy and at the same level as in arterial cord blood, whereas AVP in the venous cord blood was significantly lower and at the same level as in the maternal venous blood and in the control group. It is concluded that the fetus produces AVP and this is at least not solely caused by fetal asphyxia or related to parturition.

Distribution of vasopressin and oxytocin in rat brain.

Arginine-vasopressin and oxytocin in various portions of rat brain were determined by radioimmunoassays. The hormones were extracted from tissue samples into 0.1 N HCl and then purified partially with acetone-petroleum ether extraction. The non-equilibration method was used for the assays. In this method recovery rates of arginine-vasopressin and oxytocin were 73.0 +/- 4.4% and 75.0 +/- 3.8%, respectively. Sensitivities of the assays were 1 pg of arginine-vasopressin and 0.75 pg (0.3 microU) of oxytocin per assay tube. The higher concentrations of arginine-vasopressin and oxytocin were confirmed in the hypothalamo-neurohypophyseal system, where these hormones are synthesized, transported and stored. Relatively high concentrations of these hormones, especially oxytocin, were detected in spinal cord. Amygdala, hippocampus, limbic forebrain and pineal body contained a certain amount of arginine-vasopressin (2-20 pg/mg protein). Oxytocin (1-7 pg/mg protein) was also detected in amygdala, pons and medulla oblongata, pineal body and midbrain. The low concentrations of these hormones were also found in cerebral cortex and cerebellum.

Removal of immunoreactive arginine vasopressin by the perfused rat liver.

To assess the ability of the liver to remove immunoreactive arginine vasopressin (AVP) from the circulation and to determine the effect of certain metabolic factors on the process, a study was carried out with rat livers perfused at 37 C with an oxygenated albumin--electrolyte solution containing AVP (117 +/- 4.5 muU/ml). In controls, the hepatic clearance of AVP was 795 +/- 120 microliter/min (SEM). The addition of AVP in concentrations up to 9029 microU/ml, perfusion with a glucose-free medium, or perfusion without oxygen did not significantly alter the hepatic clearance of AVP. However, perfusion with cold medium (11 C) significantly altered AVP removal in that initially AVP removal increased, while later on AVP removal became completely inhibited. This phenomenon may possibly be a consequence of a cold-induced increase in hepatic AVP trapping which is rapidly saturated due to a cold-induced depression of AVP transport and degradation. Support for this thesis was provided by finding that high AVP concentrations depressed the cold-endhancing removal phase.

In Vitro Analysis of the Participation of Oxytocin and Vasopressin in the Gonadotropin Releasing Hormone-Induced Release of LH

SummaryThe pituitary perfusion technique was used to investigate the possible interaction between the neurohypophyseal hormones and gonadotropin releasing hormone (GnRH). The perifusion of rat anterior pituitaries with 0.2 mU/ml arginine vasopressin (AVP) resulted in a significant (P < 0.05) increase in LH release over baseline, while higher doses had no effect. When combined with GnRH, this and higher concentrations of AVP did not alter the GnRH-induced release of LH. Three concentrations of oxytocin (OT): 0.02, 0.2 and 20 mU/ml, increased baseline secretion of LH (P < 0.05) while 2 mU/ml OT did not. When added to GnRH-containing perifusion media, 0.02 mU/ml OT caused significant (P < 0.05) enhancement and prolongation of the LH response to GnRH. All higher concentrations of OT and one concentration that was tenfold lower, did not exhibit potentiating effects. When the pituitary tissue was pretreated with AVP or OT prior to stimulation with GnRH, only the same concentration of OT (0.02 mU/ml) was effecti...