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Direct cardiac stimulation by arginine vasotocin in bullfrogs (Rana catesbeiana).

The antidiuretic and vasopressor effects of arginine vasotocin (AVT) in bullfrogs have been well documented. However, the direct cardiac stimulatory effects of AVT have not been previously reported. We found that AVT stimulates significant increases in heart rate, pulse pressure, and the maximal time derivative of ventricular pressure in anesthetized bullfrogs after the beta-adrenergic and muscarinic receptors in the heart were blocked by atropine and propranolol. In spontaneously beating isolated frog atria, AVT increased the beating rate by 20% and the contractile force by 100%. The inotropic effect of AVT was also demonstrated in electrically driven atria and ventricles. Propranolol was ineffective in blocking these cardiac responses in vitro. The Hill coefficients of the concentration-response curves did not differ from unity. In conclusion, AVT possesses both positive chronotropic and inotropic effects in bullfrogs, Rana catesbeiana, probably by direct stimulation of its specific receptors in the heart.

Animals↗

Vascular effects of arginine vasotocin in toad skin.

Fluid balance in amphibians is regulated, in large part, by arginine vasotocin (AVT). One important action of this hormone is to facilitate water uptake by increasing the water permeability of the skin. Cutaneous blood flow also affects water uptake, but the effects of AVT on skin perfusion are unknown. This study tested the hypothesis that AVT facilitates water uptake, not only by increasing cutaneous water permeability, but also by promoting cutaneous blood flow. The effects of AVT on blood flow through the ventral pelvic skin, a region specialized for water uptake, were assessed in Bufo marinus by determining the conductance of the skin to acetylene (GsAc), an index of cutaneous blood flow. A pump-perfused skin preparation was used to study the effects of AVT on the cutaneous vascular resistance (CVR) of the ventral pelvic skin and the dorsal skin (a region not normally involved in water uptake). Bolus AVT injections (iv) of 10 pmol/kg and below had no significant effect on GsAc (P > 0.45). However, 100 and 300 pmol/kg of AVT decreased GsAc by 39 +/- 7 (P < 0.001) and 63 +/- 6% (P < 0.001), respectively. The higher AVT doses increased mean arterial pressure. AVT increased CVR in both pump-perfused preparations. The lowest concentration of AVT tested that significantly raised CVR was 1 x 10(-10) M for the dorsal skin (P = 0.006) and 3 x 10(-10) M for the ventral pelvic skin (P = 0.038).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Renal response of roosters with diabetes insipidus to infusions of arginine vasotocin.

In a strain of white Leghorn chicken with symptoms of hereditary diabetes insipidus (DI) and with elevated circulating levels of the antidiuretic hormone arginine vasotocin (AVT), we investigated whether the defect is based on nonfunctional endogenous AVT or on a diminished renal response to AVT. DI chickens responded to hyposmotic infusions with a higher urine flow and lower glomerular filtration rate (GFR) than healthy control birds. Urine osmolality, fractional excretion, and clearance of sodium were lower in DI birds while potassium values were similar in both groups. Hence, the high urine flow rates of the DI birds were predominantly based on a water diuresis. When infused with AVT, the GFR and the urine flow of the control birds decreased and urine osmolality increased, showing both glomerular and tubular effects of AVT. During AVT infusion, the GFR of DI birds increased, urine flow decreased only moderately, and urine osmolality was half that of the control birds. In control birds, the clearance of sodium was unchanged, whereas that of potassium decreased. In DI birds, which experienced a strong natriuresis, the clearance of both sodium and potassium increased. These data suggest that the sensitivity of the DI birds to AVT is reduced at the tubular level. The AVT-induced increase in GFR may be related to vascular effects of high AVT doses, added to the already high basal AVT level of the DI birds, in combination with an imbalance in the function of V1 and V2 receptor subtypes in these chickens.

Animals↗

Glomerular actions of arginine vasotocin in the in situ perfused trout kidney.

Recent measurements of plasma arginine vasotocin (AVT) in teleost fish suggest circulating concentrations of 10(-10)-10(-12)M. Previous studies of the renal actions of AVT in vivo suggest both diuretic and antidiuretic effects, but at unknown circulating concentrations. We have investigated the renal actions of 10(-9) and 10(-11) M AVT in vitro using an in situ perfused kidney preparation of rainbow trout (oncorhynchus mykiss). AVT increased vascular resistance (56%), reduced perfusate flow (P < 0.001), and increased interrenal aortic pressure (P < 0.001). AVT resulted in dose-dependent decreases in urine flow rates, glomerular filtration rates, and tubular transport maxima for glucose. AVT at 10(-11) M reduced relative free water clearances (P < 0.01), but urine/plasma inulin ratios were unchanged, whereas 10(-9)M AVT reduced urine/plasma inulin ratios (P < 0.01) and increased relative free water clearances (P < 0.05). The filtering population of glomeruli was reduced by both 10(-11) and 10(-9)M AVT to approximately one-third of the glomeruli, and a similar population of arterially perfused but nonfiltering glomeruli emerged. These results demonstrate that physiological concentrations of AVT have potent glomerular antidiuretic action in the trout, reducing the number of functional glomeruli, and imply reduced individual nephron filtration rates.

Animals↗

Antipyretic effect of arginine vasotocin in toads.

Arginine vasotocin (AVT) is a nonmammalian analog of the mammalian hormone arginine vasopressin (AVP). These peptides are known for their antidiuretic and pressor effects. More recently, AVP has been recognized as an important antipyretic molecule in mammals. However, no information exists about the role of AVT in febrile ectotherms. We tested the hypothesis that AVT is an antipyretic molecule in the toad Bufo paracnemis. Toads equipped with a temperature probe were placed in a thermal gradient, and preferred body temperature was recorded continuously. A behavioral fever was observed after lipopolysaccharide (LPS) was injected systemically (200 microg/kg). Systemically injected AVT (300 pmol/kg) alone caused no significant change in body temperature, but abolished LPS-induced fever. Moreover, a smaller dose of AVT (10 pmol/kg), which did not affect LPS-induced fever when injected peripherally, abolished fever when injected intracerebroventricularly. We therefore conclude that AVT plays an antipyretic role in the central nervous system, by means of behavior, in an ectotherm, a fact consistent with the notion that AVT/AVP elicits antipyresis by reducing the thermoregulatory set point.

Animals↗

Arginine vasotocin and glomerular filtration rate in saltwater-acclimated ducks.

We examined the relationship between whole kidney glomerular filtration rate (GRF) and the plasma concentration of immunoreactive arginine vasotocin (AVT), the avian antidiuretic hormone, in saltwater-acclimated ducks. During steady-state diuresis, driven by infusion of sodium chloride solutions, transient reductions of [14C]inulin clearance (3 ml X min-1 X kg-1) occurred when plasma AVT concentrations were roughly doubled by systemic injection of synthetic AVT or after stimulation of endogenous AVT release by perfusion of the third ventricle with hypertonic artificial cerebrospinal fluid (CSF). Transient increases in GFR occurred when plasma AVT was reduced during inhibition of its endogenous release by hypotonic ventricle perfusion. GFR also increased after injection of AVT antiserum but returned to control values within 30 min, while plasma AVT concentration remained very low for at least 1 day. During antidiuresis evoked by infusion of strongly hypertonic saline, GFR values estimated from plasma disappearance curves of [125I]iothalamate were not different from the GFR values estimated subsequently with the same method in the same ducks made diuretic by hypotonic saline infusions, although AVT concentrations were depressed during the latter as compared with the former infusion. Factors other than AVT must be important for the control of GFR during sustained osmotic stress.

Adaptation, Physiological↗

Hypothalamic arginine vasotocin mRNA abundance variation across sexes and with sex change in a coral reef fish.

Gonadal hormones are important mediators of sexual and aggressive behavior in vertebrates. Recent evidence suggests that the peptide hormones arginine vasotocin (AVT) and its mammalian homologue arginine vasopressin (AVP) often critically mediate these gonadal hormone effects on behavior and have direct influences on behavioral variation. Behavioral differences between sexes, across reproductive states, and even among closely related species are correlated with differences in central AVT/AVP systems in many species. We report differences in hypothalamic AVT mRNA levels between distinct alternate male phenotypes and with female-to-male sex change in the bluehead wrasse (Thalassoma bifasciatum), a teleost fish. The aggressively dominant and strongly courting male phenotype has greater numbers of AVT mRNA producing cells in the magnocellular preoptic area of the hypothalamus than females. Levels of AVT mRNA within these cells in dominant males are also approximately three times female levels whereas the non-aggressive male phenotype has AVT mRNA levels approximately twice female levels. Behavioral sex change is very rapid in this species and is not dependent on the presence of gonads. Conversely, rapid increases in sexual and aggressive behavior during sex change are closely paralleled by approximate fourfold increases in hypothalamic AVT-mRNA levels. The behavioral plasticity shown by bluehead wrasses in response to social environment might be mediated in part by a neuropeptide, AVT, with changes in the gonads and gonadal hormones as the result rather than the cause of behavioral dominance.

Animals↗

Arginine vasotocin interacts with the social environment to regulate advertisement calling in the gray treefrog (Hyla versicolor).

Arginine vasotocin (AVT) has different effects on social behaviors across species with different social systems. However, less attention has been directed towards the way environmental stimuli interact with AVT to affect social behaviors. Previous work found that AVT affects the production of advertisement calls and the outcome of competitive interactions between male gray treefrogs (Hula versicolor). We conducted a field study to investigate how the presence of other males in a chorus influenced the production of advertisement calls in males treated with AVT or saline. After hormone treatment we placed individuals in call sites either within 50 cm of another calling male (proximate), or more than 2 m away from any calling male (distant). Males treated with AVT produced significantly longer calls with more pulses when placed at proximate call sites, but not distant call sites. Nonsignificant trends indicated that these increases in call length coincided with a decrease in call rate. There was no effect of call site distance on advertisement calls when males were treated with saline. These results indicate that the social environment can modulate the action of AVT on an important reproductive behavior, and that AVT does not influence call duration and pulse number unless another male is nearby. Understanding how social stimuli regulate the action of AVT on behavior could provide insight on the diversity of AVT function across species.

Animals↗

Circannual analysis of pineal gland indoles and vasotocin-like immunoreactivity in male rats kept on constant photoschedules and temperature.

Levels of vasotocin-like immunoreactivity (iVT) and the indoles serotonin (5HT), 5-hydroxyindole acetic acid, N-acetyl-serotonin (NAS) and melatonin were measured over 24-hour periods at monthly intervals in the pineal gland of male rats kept under constant laboratory conditions of photoperiod and temperature. The 8- to 10-fold increase in pineal iVT, which occurred during mid-August, was not related to variations over the 24-hour light:dark (L:D) cycle. Tryptophan and 5HT exhibited seasonal variations over the 24 h L:D cycle with a single peak during the winter months. Twenty-four-hour levels of NAS tended to increase during the fall and spring. Seasonal effects on indole metabolism were further suggested by a marked decline during the fall in the correlation between NAS versus melatonin in individual pineal glands. Positive correlations between 5HT versus NAS and 5HT versus melatonin tended to be significant only during the summer months. These data suggest that environmental cues other than photo-period and temperature can regulate pineal neuroendocrine functions.

Animals↗

Vasotocin biosynthesis by neurohypophysial cells from human fetuses. Evidence for its ependymal origin.

Cultured neurohypophysial cells from human fetuses aged 130-155 days release into the culture medium an active principle which has antidiuretic, hydroosmotic and rat uterine activities. The chromatographic mobility of the active principle, as well as the susceptibility of all of the above activities to tryptic digestion, indicates the presence of a basic peptide identical to arginine vasotocin (AVT). The ability of these cultured cells, which are probably ependymal cells, to release the above activities during 43 days of incubation, suggests that AVT is synthesized and secreted by specialized ependymal cells in the developing human neurohypophysis. Neither in the culture media from anterior pituitaries of the same fetuses nor in control culture media could antidiuretic, rat uterine or hydroosmotic activities be detected. Although the nonincubated neurohypophyses of the same age contain pharmacological activities suggesting the presence of vasopressin, oxytocin and AVT, the neurohypophysial cells cultured in vitro apparently release only AVT into the medium. This supports the suggestion that whereas vasopressin and oxytocin are synthesized in the hypothalamic neurosecretory cells, AVT, on the contrary, appears to be synthesized by ependymal neurohypophysial cells in the developing human neurohypophysis. Consequently, the fetal human neurohypophysis, and presumably the fetal mammalian neurohypophysis, appears not only as a storage site for neurohypophysial hormones but also as an endocrine structure which synthesizes and secretes AVT by ependymosecretion.

Ependyma↗

Stimulation of rat prolactin secretion in vivo by arginine vasotocin: influence of age of solution, nighttime administration, and dose.

In male rats pretreated for 3 days with 50 microgram of estradiol benzoate (E) and 25 mg of progesterone (P), the i.v. administration of 1 microgram of arginine vasotocin (AVT) from solutions that were 0, 6, 24 or 48 h old caused a significant rise in plasma prolactin (Prl) 10 min after injection. In the 2nd experiment, the i.v. injection of 1 microgram AVT into EP-primed adult male rats at either 01:00 (during darkness) or 13:00 h (during light) resulted in a significant and similar elevation in plasma Prl levels. In the 3rd experiment, normal adult male rats under urethane anaesthesia were given an i.v. injection of diluent or of 100 ng, 1 microgram or 10 microgram AVT. A significant rise in plasma Prl was observed at 10 and 20 min following injection only in the group treated with 1 microgram AVT. In none of these experiments did AVT alter the content of pituitary Prl.

Animals↗

Arginine vasotocin immunoreactivity in hypothalamic and extrahypothalamic areas of an amphibian brain.

The distribution of arginine vasotocin immunoreactivity (irAVT) was investigated in the brain of male rough-skinned newts (Amphibia: Taricha granulosa) using microdissection and radioimmunoassay techniques. The highest levels of irAVT were observed in the neuroendocrine hypothalamo-hypophysial system. However, detectable quantities of irAVT (greater than 0.40 ng/mg protein) also were observed in extrahypothalamic areas such as pallium, amygdala, striatum and thalamic, tectal and brainstem nuclei. No irAVT was detected in the olfactory bulb, rostral telencephalon, or in specific areas of the caudal telencephalon and diencephalon. These results indicate that, in amphibians, AVT is distributed among a wide range of brain areas and that there is regional specificity in irAVT concentrations.

Animals↗

Gonadal steroid modulation of vasotocin concentrations in the bullfrog brain.

Concentrations of the neuropeptide arginine vasotocin (AVT) are sexually dimorphic in some regions of the bullfrog brain. Since these differences in AVT content may be due to sexual differences in plasma steroid concentrations, we performed a gonadectomy-steroid replacement experiment (30-day treatment) to assess the effects of specific steroids on AVT concentrations (determined by RIA) in adult male and female bullfrogs (Rana catesbeiana). These treatments had significant effects in six brain areas. Gonad removal decreased AVT concentrations in the amygdala pars lateralis, septal nucleus and habenula of both sexes. Gonadectomy decreased AVT content in optic tectum, torus semicircularis and pretrigeminal nucleus of males only. Dihydrotestosterone treatment resulted in AVT concentrations at or above sham levels in all six areas, whether or not gonadectomy decreased content. Estradiol fully restored AVT concentrations only in the septal nucleus and habenula (of both sexes) and in the amygdala of females. Estradiol partially restored AVT levels in the amygdala of males. These results indicate that the gonads maintain AVT concentrations in several brain areas and that steroids can modulate levels of AVT in bullfrog brain. Effects of each steroid vary depending upon the region and sex of the frog. AVT cells are present in three of these regions--the amygdala pars lateralis, septal nucleus and pretrigeminal nucleus. Steroids may be directly affecting AVT synthesis in these cells and these populations may be the source of AVT fibers in the other steroid-sensitive areas.

Animals↗

Prolactin-releasing activity of arginine vasotocin in vitro.

A significant elevation in both luteinizing hormone (LH) and prolactin release was observed in the culture medium of hemipituitaries from castrated estrogen-progesterone (EP) primed female rats incubated for 5 h with arginine vasotocin (AVT) and luteinizing hormone-releasing hormone (LRH) compared to corresponding halves incubated with LRH alone. However, AVT alone did not significantly alter the discharge of LH or prolactin from hemipituitaries of EP-treated rats in vitro. Arginine vasopressin, a natural analogue of AVT, inhibited prolactin release using this same model system. Normal male rat hemipituitaries incubated with AVT released significantly more LH and prolactin into the culture medium than did their corresponding halves. A log-dose response curve indicated that any dose from 100 ng to 10 mug AVT significantly promoted prolactin release. However, the terminal tripeptide of AVT, Pro-Arg-Gly(NH2), failed to modify the discharge of LH or prolactin into the culture medium.

Animals↗

Failure to demonstrate antigonadotrophic activities of arginine vasotocin in the mouse.

Arginine vasotocin (AVT) has previously been proposed to be a pineal hormone which reduces reproductive competency in mammals. The effects of AVT on the growth of immature reproductive organs of the mouse have been studied using blind study techniques. Evidence is presented which fails to support the proposed role of AVT as a mammalian antigonadotrophin.

Animals↗

Acute effects of arginine vasotocin on plasma and pituitary levels of prolactin in the male rat: influence of urethane anesthesia.

The acute effects of arginine vasotocin (AVT), a putative pineal peptide, on plasma levels of prolactin were investigated in the unanesthetized, estrogen-progesterone-treated male rat. A 10-microgram s.c. injection resulted in significantly increased levels of prolactin while a 1-microgram injection depressed plasma levels of this hormone; an inhibition of release was further suggested by increased levels of pituitary prolactin in rats treated with the lower dose. The same dose administered subcutaneously to urethane-anesthetized rats had no significant effect on plasma prolactin titers while a 10-microgram dose was still stimulatory. In anesthetized rats, no dose of the AVT administered (1 ng to 10 micrograms, s.c., or 1 fg to 1 microgram, i.v.) resulted in inhibition of prolactin release. In the unanesthetized normal male rat, 5 micrograms AVT first increased and then decreased levels of prolactin. Urethane anesthesia appears to mask an inhibitory effect of AVT on plasma prolactin levels in these animal preparations. Since AVT is capable of decreasing plasma prolactin levels, this peptide might be involved in the depression of plasma prolactin levels which appears to (at least partially) mediate pineal-induced gonadal degeneration.

Anesthesia↗

Arginine vasotocin in ovine fetal blood, urine, and amniotic fluid.

Arginine vasotocin ([8-arginine]-oxytocin) (AVT), the primary antidiuretic principle in submammalian vertebrates, has been reported to be present in mammalian pituitary and pineal glands. Although the most phyletically ubiquitous of the known neurohypophysial peptides, AVT is still not recognized as a mammalian hormone. We examined plasma, urine, and amniotic fluid from fetal lambs by radioimmunoassay (RIA) for evidence of AVT to assess the possibility of its being such a hormone. Measureable quantities of AVT-like immunoreactivity (irAVT) were observed in fetal plasma (2.4 +/- 0.2 pg/ml), urine (1.4 +/- 0.2 pg/ml), and amniotic fluid (1.9 +/- 0.2 pg/ml). Since the AVT antiserum shows minimal cross-reactivity with arginine vasopressin (AVP) and oxytocin (OT), measurements of AVP and OT concentrations in the same biological fluids also were conducted with specific antisera. The results suggest that the irAVT was not accountable on the basis of cross-reaction. To further verify the identity of the irAVT, a high pressure liquid chromatography system using RIA as a means of detection was developed. This system is sufficiently sensitive to allow the separation and quantitation of picogram quantities of the synthetic peptides AVT, AVP, and OT. In this system, the irAVT in fetal plasma, urine, and amniotic fluid appeared as a single peak coeluting with synthetic AVT. These results indicate that AVT is present in ovine fetal plasma and support the view that the fetus secretes this peptide. The physiological significance of circulating AVT remains to be defined.

Amniotic Fluid↗

Fetal neurohypophyseal arginine vasopressin and arginine vasotocin in man and sheep.

Immunoreactive arginine vasopressin (AVP) and arginine vasotocin (AVT) were quantitated in 15 of 17 human fetal pituitary glands early in gestation (11-19 weeks) and in 8 of 9 ovine fetal pituitary glands late in gestation (109-137 days). In 14 of 15 human fetal glands, AVT content exceeded that of AVP. There was a significant rise of AVP (as a percentage of total AVP plus AVT content) with gestational age over the period of 12-19 weeks (P less than 00.01). The ovine fetal glands demonstrated a preponderance of AVP over AVT. The mean AVP and AVT content in the ovine glands was 5.7 +/- 2.9 and 0.8 +/- 0.2 mU/mg gland weight, respectively, compared with the values in the human fetal pitiutaries, 0.8 +/- 0.2 and 1.2 +/- 0.2 mU/mg gland weight, respectively. The relative percentage of AVP and AVT in the ovine fetal pituitaries was 76.0+/- 9.6% and 23.9 +/- 9.6%, respectively, as contrasted to the human fetal glands, 36.7 +/- 2.7% AVP and 63.3 +/- 2.7% AVT. The preponderance of AVT over AVP in the early gestational age mammalian fetus may represent a primative first step in molecular evolution of the neurohypophyseal peptides.

Animals↗