Effect of vasopressin on neuronal responses of theNucl. Caudalis of the spinal trigeminal tract in rats

Effect of vasopressin on responses of individual neurons of thenucl. caudalis of the spinal trigeminal tract was studied on rats under urethan anesthesia; the responses were evoked by nociceptive (stimulation of the tooth pulp) or non-nociceptive (stimulation of Aa fibers of the infraorbital nerve) afferent activation. After injection of 10 nM vasopressin into the recording zone, responses evoked by stimulation of the tooth pulp were suppressed in all studied neurons of the high-threshold group; the same was true as to responses induced by stimulation of the tooth pulp and infraorbital nerve in most neurons of the convergent group. At the same time, vasopressin did not change the responses evoked by stimulation of Aa fibers of the infraorbital nerve in neurons of the low-threshold group. Possible involvement of vasopressin in the process of pain suppression is discussed.     

Effects of vasopressin and corticosterone on fatty acid metabolism and on the activities of glycerol phosphate acyltransferase and phosphatidate phosphohydrolase in rat hepatocytes.

The effects of vasopressin on the short-term control of fatty acid metabolism were studied in isolated rat hepatocytes. Vasopressin increased the oxidation of oleate to CO2 and decreased the formation of ketones in hepatocytes from Wistar rats, but not from Brattleboro rats. Incubation with vasopressin for 30 min increased the conversion of oleate into triacylglycerol by 17% and 32% in hepatocytes from Wistar and Brattleboro rats respectively. The corresponding increases for the phospholipid fraction were 19% and 42%. When Wistar-rat hepatocytes were incubated with corticosterone for 6 h there was a 19% increase in triacylglycerol synthesis, and a 52% increase if vasopressin was added 30 min before the end of the incubation. Glycerol phosphate acyltransferase activity was not significantly increased by vasopressin. Incubation for 5-60 min with vasopressin increased the Vmax. of phosphatidate phosphohydrolase by 48% and 32% respectively in hepatocytes from Wistar and Brattleboro rats. These increases were antagonized if EGTA was added to the medium used for incubating the hepatocytes. The replacement of vasopressin by 5 microM-ionophore A23187 produced a significant increase of 13% in the phosphohydrolase activity. It is therefore likely that the effects of vasopressin on the phosphohydrolase are mediated by Ca2+. These results are discussed in relation to the possible function of phosphatidate phosphohydrolase in controlling the turnover of phosphoinositides, the synthesis of phosphatidylethanolamine, phosphatidylcholine and triacylglycerol, and the secretion of very-low-density lipoproteins.     

下丘脑室旁核加压素能神经元参与电针刺激对实验性...

It has been demonstrated in animal model of somatic pain that hypothalamic paraventricular nucleus (PVN) participates in acupuncture analgesia, probably by mediation of vasopressin release. The role of PVN in acupuncture analgesia for experimental visceral pain in rats was further investigated in the present study. Experimental results demonstrated that electroacupuncture could inhibit the writhing response, produced by intraperitoneal injection of antimonium potassium tartrate and this inhibitory effect could be enhanced by electrical stimulation of PVN, but decreased by electrolytical lesion of PVN, intracerebroventricular injection of vasopressin antiserum (14 microliters) or the vasopressin antagonist, d(CH2)5Tyr(Me)-AVP (500 ng/5 microliters). Intraperitoneal administration of the latter drug (10 micrograms/kg), however, was ineffective. The above experimental results suggest that vasopressinergic neurons in PVN also participate in the inhibition of visceral pain by electroacupuncture.     

Vasopressin affects the behavior of rats in a positively-rewarded discrimination task

The effects of subcutaneous injections of vasopressin were investigated in a study utilizing 72 male Long-Evans rats trained in an appetitive black-white discrimination T-maze task. Animals which were reinforced for choosing the black goal arm demonstrated prolonged extinction if they received vasopressin prior to daily extinction sessions. This effect was not observed in animals reinforced for choosing the white goal arm. Prolonged extinction was not found in animals which received vasopresson only during acquisition or in control animals which received saline. Speed and activity scores did not differentiate the groups. These results demonstrate that vasopressin can affect the behavior of rats on a positively-reinforced task.     

Immunocytochemical evidence for the presence of a mutant vasopressin precursor in the supraoptic nucleus of the homozygous Brattleboro rat

Summary CP-14, a tetradecapeptide from the predicted mutant vasopressin precursor in the homozygous Brattleboro rat was detected immunocytochemically in the supraoptic nucleus of homozygous Brattleboro but not normal rats. The staining was localized to the periphery of the perikarya. CP-14 immunoreactivity was not found in the neural lobes, paraventricular nuclei, accessory nuclei or suprachiasmatic nuclei of either homozygous Brattleboro or normal rats. Vasopressin immunoreactivity was found in the neural lobe and in the perinuclear region of neurons of the supraoptic, paraventricular, suprachiasmatic and accessory nuclei of normal rats. Vasopressin immunoreactivity was also found in homozygous Brattleboro rats, mainly in the ventral part of the supraoptic nucleus: densely stained solitary cells were found amongst other faintly stained perikarya. In both cell-types the staining was mainly in the periphery of the perikarya. No vasopressin immunoreactivity was detected in the paraventricular nuclei, suprachiasmatic nuclei, accessory nuclei or neural lobe of homozygous Brattleboro rats.CP-14 and vasopressin immunoreactivities were found to be co-localized; both were present in the periphery of the same perikarya of the supraoptic nuclei of homozygous Brattleboro rats. Differential staining was found with antioxytocin serum in both normal rats and homozygous Brattleboro rats: separate neurons were stained for either oxytocin or vasopressin and CP-14. Immunoreactive oxytocin was found mainly in the perinuclear region of the neurons from the supraoptic, paraventricular and accessory nuclei.     

Effect of ACTH 4-10 on passive avoidance of rats lacking vasopressin (Brattleboro strain).

The hypothesis that the effects of ACTH 4-10 on avoidance are mediated via the release of endogenous vasopressin was investigated. To test this hypothesis, we observed the effect of ACTH 4-10 on the passive avoidance of Brattleboro rats with diabetes insipidus resulting from a total genetic deficiency of vasopressin (DI) and Brattleboro rats without diabetes insipidus (HE). Normal Long-Evans rats (LE) were also included for comparison purposes. The results did not support the hypothesis. ACTH 4-10 did influence the passive avoidance of DI rats; this should not have occurred if the release of endogenous vasopressin is necessary for ACTH 4-10 to influence avoidance.     

Age-dependent DOCA-salt hypertension in Brattleboro rats: the role of vasopressin

The age-dependent participation of endogenous vasopressin (VP) during the development of DOCA-salt hypertension was studied in young (28-day-old) and adult (75-day-old) Brattleboro rats. VP-deficient homozygous (DI) rats were compared to heterozygous (non-DI) littermates which do synthetize VP. Six weeks of DOCA-salt treatment did not increase blood pressure (BP) in adult DI rats. On the other hand, in young DI animals there was a significant rise of systolic and mean arterial pressure accompanied by the hypertrophy of the left ventricle. This moderate DOCA-salt hypertension of young DI rats contrasted with severe hypertension of young non-DI rats. Increased BP response of young VP-deficient DOCA-salt treated rats was independent of the saline intake or blood volume expansion which were similar in young hypertensive and adult normotensive DI animals. It could be concluded that vasopressin is not essential for the induction of DOCA-salt hypertension in young rats even if VP is responsible for the magnitude of BP elevation. In contrast to young animals vasopressin is very important for the development of DOCA-salt hypertension in adult rats.     

Prenatal administration of arginine vasopressin impairs memory retrieval in adult rats

Eight pregnant female rats were chronically treated via an osmotic pump with arginine vasopressin or placebo during days 13 to 19 gestation. All offspring were tested as adults in either a discrimination task or a 25 day retention of a passive avoidance response. The results revealed that rats whose mother had been treated with vasopressin did not differ from controls on the acquisition or reversal of a brightness discrimination; however, they did require more trials to reach criterion during the ten day memory test of discrimination reversal. Further, treatment resulted in impaired memory retrieval in male rats on the 25 day memory test, while female rats were not affected. Treatment did not influence body weight. The results indicated that vasopressin administered during the prenatal period of development may have had a teratogenic effect on memory retrieval.     

Inhibitory roles of the hypothalamic atrial natriuretic polypeptide on the vasopressin release in the sodium-loaded rats

Implication of the brain atrial natriuretic polypeptide on the vasopressin release was investigated using rats fed with a high-sodium containing diet. Sodium loading increased not only the blood pressure but also the urinary output of vasopressin significantly. The plasma vasopressin concentration increased about 10 times after the intracerebroventricular injections of angiotensin II. Thereby, magnitude of the response was significantly smaller in the rat fed with a high sodium diet than in rats with the regular-diet. The hypothalamic content of both vasopressin and atrial natriuretic polypeptide was significantly larger in the high-salt group than the regular-salt. The intraventricular injections of atrial natriuretic polypeptide abolished the vasopressin release induced by the intraventricular injections of angiotensin II. These results indicate that the vasopressin production in the hypothalamus is increased, but the release is relatively suppressed in the sodium-loaded rats, and that increased hypothalamic atrial natriuretic polypeptide is involved in the suppression of the vasopressin release and in decreasing their sodium appetite to avoid the high sodium environment.     

Thyroid stimulating effect of exogenous vasopressin and oxytocin in hypophysectomized rats during immobilization stress

Male Wistar rats were hypophysectomized 1 week before restraint stress. The hypophysectomy caused a decrease of blood vasopressin (30%, P less than 0.05) and a diminution of the thyroid activity (the thyrocyte height lowered to 43%, P less than 0.01). The TSH concentration was about normal and remained constant during the experiment. After 20 min of the restraint stress, the vasopressin concentration reached 178% (P less than 0.01), but the thyroid did not response in rats with the intact hypophysis. In the hypophysectomized rats, the restraint stress caused neither essential changes of the blood vasopressin nor the thyroid function as compared with the hypophysectomized control. An injection of vasopressin (5.0 ng/100 g) or oxytocin (15.0 ng/100 g) resulted in a slight activation of the thyroid in the hypophysectomized rats but significantly stimulated in when combined with the restraint stress; vasopressin injection led to an increase of the thyrocyte height to 152% (P less than 0.01), oxytocin--to 126% (P less than 0.05). Thus, in hypophysectomized rats, vasopressin and oxytocin can influence the thyroid directly. Stressful conditions facilitate the thyroid stimulating effect of these nonapeptide neurohormones.     

Effect of salt loading and salt deprivation on the vasopressin and oxytocin content of the median eminence and the neural lobe in adrenalectomized rats

Summary In adrenalectomized rats the influence of salt loading or salt deprivation on the vasopressin and oxytocin content of the median eminence (ME) and the neural lobe (NL) was studied by means of various methods: (1) morphometric and microphotometric analysis of aldehyde fuchsin-stained sections of ME and NL; (2) immunohistochemical demonstration of neurophysin, oxytocin, and vasopressin in the ME and in the NL; (3) radioimmunological measurement of oxytocin and vasopressin in the ME and in the NL. Adrenalectomy in salt-substituted rats raised the vasopressin content of the outer layer of the ME (OLME) but had no influence on the amount of vasopressin in the inner layer of the ME and in the NL. Osmotic stimulation of adrenalectomized rats by hypertonic saline markedly diminished vasopressin and oxytocin in the inner layer of the ME and in the NL but did not, or only slightly reduced vasopressin in the OLME. Withdrawal of salt supplementation in adrenalectomized rats resulted in a decrease of plasma sodium and plasma volume. It did not change the vasopressin or oxytocin content of the inner layer of the ME and of the NL, but it was correlated with a decrease of vasopressin in the OLME. The present findings may suggest that vasopressin in the OLME is involved in salt and/or volume regulation by influencing the hypophysial-adrenal axis.The study was supported by the Deutsche Forschungsgemeinschaft (Bo 392/6-5¹ and SFB 90, Cardiovasculäres System, A5²). The morphometric measurements with the TAS plus were carried out at the Max-Planck-Institut für Psychiatrie, Munich, FRG. We are particularly indebted to Prof. G. W. Kreutzberg and Prof. P. Schubert for their help     

Effects of naloxone and cholecystokinin on food and water intake in vasopressin-deficient rats (Brattleboro strain)

Opioid peptides and cholecystokinin (CCK) have been shown to play a role in regulation of feeding behavior. Another neuropeptide that has recently been suggested to be involved in feeding is vasopressin. We explored possible interactions between opiates, CCK and vasopressin in feeding regulation by studying feeding suppression produced by naloxone and CCK in Brattleboro (DI) rats, which are homozygous for diabetes insipidus and lack the ability to synthesize vasopressin. Ten DI and 15 age-matched Long Evans (LE) rats were food deprived for 14 hours on two different days and then injected with naloxone (2.5 mg/kg) on one day or saline on the other. Thirty minutes later the food was returned and food and water consumption were measured after 1, 3 and 4 hr. Naloxone suppressed the food consumption of both DI and LE rats but the suppression was greater for the DI rats. This result was specific to feeding as water consumption was suppressed in LE more than in DI rats. Two weeks later, the same rats were food deprived for 6 hours on two different days and then injected with CCK-8 (2.5 micrograms/kg) on one day and with saline on the other. Food was returned one minute after the injection and food and water consumption were measured 30 and 60 minutes later. Food intake was reduced equally for both DI and LE rats. Water intake was not reduced. The results suggest that the suppression of feeding by CCK does not require an intact vasopressinergic system. The greater feeding suppression by naloxone in DI rats may suggest that opiates are interacting with vasopressin in producing their effects on food intake.     

Central cardiovascular effects of mammalian neurohypophyseal peptides in conscious rats

To confirm and extend the results of previous studies which demonstrated central cardiovascular effects of vasopressin in anesthetized rats, we determined blood pressure and heart rate changes for 30 minutes after intracerebroventricular injections of arginine vasopressin, arginine vasotocin and oxytocin in conscious rats. As compared to sham injections, significantly greater increases in either systolic or diastolic blood pressure were noted over the 30 minutes which followed the injection of 0.15, 1.0 or 10.0 nM of either vasopressin or vasotocin. In animals given vasopressin, plasma levels of the peptide were determined. There was a substantial increase in plasma vasopressin only after the highest dose. Overall blood pressure responses to doses of oxytocin as high as 100 nM were not significantly different than sham injections. Heart rate following both vasopressin and vasotocin was increased at 0.15 nM, was initially decreased then increased at 1.0 nM and was substantially decreased after the 10.0 nM dose. There was a significant increase in heart rate at the 10.0 nM and 100 nM doses of oxytocin. Dose response curves for systolic blood pressure and heart rate 20 minutes after injection were similar for vasopressin and vasotocin. We conclude that arginine vasopressin has significant central pressor and tachycardic effects in conscious rats, and it is related, at least in part, to the tail structure of the peptide, which is shared with arginine vasotocin.     

Pressor effect of centrally administered neuropeptide Y in rats: role of sympathetic nervous system and vasopressin

The haemodynamic effects of intracerebroventricular (i.c.v.) administration of neuropeptide Y (NPY) in urethane-anaesthetized rats were studied. In Sprague-Dawley rats, NPY increased both blood pressure and heart rate in a dose-dependent manner. This response was unaffected by removal of the adrenal medullae or pretreatment with a specific vasopressin antagonist (180 ng/kg i.v.), but was abolished by phenoxybenzamine (1mg/kg i.v.). After pretreatment with propranolol (1mg/kg i.v.), the tachycardia was inhibited and the pressor response was of shorter duration than in controls. In 6-hydroxydopamine treated rats (two doses of 250 micrograms i.c.v., three days apart), NPY still elicited a pressor response and tachycardia, which were significantly higher than controls 15 minutes after the injection. Plasma levels of vasopressin were not altered by i.c.v. administration of NPY. However, in Brattleboro rats the peptide had no haemodynamic effects. Our results suggest that activation of sympathetic nervous system but not release of vasopressin or adrenal catecholamines into the bloodstream mediates the cardiovascular response to NPY. Central vasopressin pathways however may be involved.     

Changes in pituitary oxytocin and vasopressin during the estrous cycle and after ovarian hormones: evidence for mediation by norepinephrine

Pituitary levels of oxytocin and vasopressin were maximal on the morning of proestrus, declined during estrus, and were lowest on metestrus in cycling female rats. Norepinephrine levels in the paraventricular nucleus were decreased on proestrus and estrus when compared with metestrus-diestrus. Norepinephrine did not vary in the supraoptic nucleus. Administration of estradiol benzoate to ovariectomized rats elevated oxytocin in the pituitary 54 hr later. This elevation was not affected by a subsequent injection of estrogen or progesterone. Estrogen priming did not affect vasopressin levels in the pituitary, but a second injection of estrogen or of progesterone 48 hr later increased vasopressin in the pituitary when measured 6 hr after the second injection. Vasopressin was decreased 30 hr after a second injection of estrogen. The ovarian hormone treatments that elevated pituitary vasopressin decreased steady state levels of norepinephrine in the paraventricular nucleus and reduced the depletion of norepinephrine after administration of the catecholamine synthesis inhibitor α-methyltyrosine, suggesting a decrease in turnover. Ovarian hormones did not affect norepinephrine in the supraoptic nucleus. The present results suggest a role for posterior pituitary hormones in reproductive processes and a role for noradrenergic mechanisms in the paraventricular nucleus in mediating the effects of ovarian steroids on pituitary vasopressin.     

Role of sodium and water excretion in the antihypertensive effect of vasopressin in the spontaneously hypertensive rat.

Mean arterial pressure (mmHg (1 mmHg = 133.322 Pa)), sodium excretion rate (mumol.kg-1.min-1), and urine flow (microL.kg-1.min-1) were measured in conscious unrestrained spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) before, during, and after a 3-h intravenous infusion of arginine vasopressin (20 ng.kg-1.min-1), an equipressor dose of phenylephrine, or an infusion of the vehicle. Cessation of the phenylephrine infusion was associated with a return of arterial pressure to preinfusion control values in both SHR and WKY. Cessation of the vasopressin infusion was also associated with a return of arterial pressure to preinfusion values in WKY. In contrast, in the SHR, arterial pressure fell from a preinfusion control level of 164 +/- 6.2 to 137 +/- 4 mmHg within 1 h of stopping the vasopressin infusion. Five hours after stopping the infusion, pressure was 134 +/- 3 mmHg (29 +/- 5 mmHg below preinfusion levels). Similar to the WKY, cessation of a vasopressin infusion was associated with a return of arterial pressure to preinfusion values in Sprague-Dawley rats. Thus, the failure to observe a hypotensive response in normotensive rats was not a peculiarity of the WKY strain. Sodium excretion rates increased during the infusions of vasopressin to a greater extent in SHR than in WKY. However, the natriuresis induced by phenylephrine was not significantly different from that generated by vasopressin in SHR, and in WKY, the natriuresis was greater for phenylephrine than for vasopressin. Urine output increased to a greater extent during the infusions of phenylephrine in both SHR and WKY than during vasopressin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antinociceptive effects of intraventricular or systemic administration of vasopressin in the rat

The effects of intraventricular administration of lysine-vasopressin on pain sensitivity in the rat were determined in the tail-flick test. Vasopressin (16–100 μg) was found to induce potent and dose-dependent antinociceptive actions, lasting up to one hour. An additional experiment demonstrated that analgesia induced by vasopressin was not blocked by naloxone, suggesting that this analgesia is independent of opiate receptor systems. Vasopressin was also found to be equally effective in elevating tail-flick latency after systemic administration. These results, together with others, suggest a possible role of vasopressin systems in the regulation of pain sensitivity.     

Different effects of chronic Na+, Cl−, and K+ depletion on brain vasopressin mRNA and plasma vasopressin in young rats

1. We studied the effects of selective chronic dietary sodium, chloride, or potassium depletion in young rats on vasopressin mRNA levels in the supraoptic and paraventricular nuclei, an index of vasopressin formation, and in plasma vasopressin levels, an index of vasopressin release. 2. All diets significantly increased plasma renin activity, contracted the extracellular fluid volume, and decreased serum osmolarity. 3. In the supraoptic nucleus, vasopressin mRNA levels were significantly decreased in the low-sodium group but were not significantly affected by chloride depletion. 4. There were no significant changes in vasopressin mRNA in the paraventricular nucleus after sodium or chloride dietary depletion. 5. After 2 weeks of potassium depletion, vasopressin mRNA levels were decreased in the supraoptic nucleus. When potassium depletion was prolonged for 3 weeks, vasopressin mRNA levels increased in both supraoptic and paraventricular nuclei. 6. Plasma vasopressin levels were high in animals subjected to dietary chloride depletion or to 3 weeks of potassium depletion. Dietary sodium depletion or 2 weeks of dietary potassium depletion did not significantly affect plasma vasopressin. 7. Our results show that chronic sodium, chloride, or potassium depletion differentially affect brain vasopressin mRNA and vasopressin release in young rats. 8. The effect of these diets may be mediated through changes in the extracellular fluid volume, serum osmolarity, and/or renin angiotensin system.     

beta-Endorphin controls vasopressin release during foot shock-induced stress in the rat

This study tested the possibility that beta-endorphin is involved in the regulation of vasopressin release during stress induced by inescapable electric foot shock. To this end, a specific anti-beta-endorphin antiserum or a control serum lacking the specific anti-beta-endorphin antibodies was administered to male rats. Plasma vasopressin concentrations, measured by radioimmunoassay, were not affected by brief foot shock stress in control rats, but were raised significantly by the stress in animals which had received an intracerebroventricular (i.c.v.) injection of the anti-beta-endorphin antiserum. In contrast, when the same volume of the anti-beta-endorphin antiserum was injected into a tail vein, foot shock stress produced only a slight effect on vasopressin release. I.c.v. injection of the antiserum changed neither basal nociceptive threshold nor stress-induced analgesia as revealed by the tail-flick latency. Vasopressin release induced by an osmotic stimulus was not influenced by the anti-beta-endorphin antiserum given i.c.v. The opiate antagonist naloxone or the glucocorticoid dexamethasone raised plasma vasopressin concentration in stressed rats which had received the control serum (i.c.v.); however, after i.c.v. injection of the anti-beta-endorphin antiserum neither naloxone nor dexamethasone elevated the plasma vasopressin concentration beyond the level reached by the anti-beta-endorphin antiserum (i.c.v.) alone. These results suggest that beta-endorphin inhibits the release of vasopressin during foot shock-induced stress in the rat.     

Possible influence of tachykinins on body fluid homeostasis in the rat

The effect on water intake, urine flow and vasopressin release of intracranial injections of substance P, physalaemin and eledoisin was studied in Wistar and Brattleboro, homozygous and heterozygous, rats. The tachykinins strongly inhibited water intake both in Wistar and in Brattleboro, homozygous and heterozygous, rats. Physalaemin and eledoisin reduced urine flow in Wistar and heterozygous, but not in homozygous, Brattleboro rats. Substance P never affected urine elimination. Physalaemin and eledoisin produced a dose-dependent, long lasting release of vasopressin in Wistar rats. Substance P did not affect the release of vasopressin. The results suggest that both substance P and physalaemin could influence brain mechanisms which control water intake, acting as thirst inhibitors, and that physalaemin could also participate in body fluid control by conserving water through vasopressin release.