Sex differences in the cardiovascular and renal actions of vasopressin in conscious rats

1997 ◽  
Vol 272 (1) ◽  
pp. R370-R376 ◽  
Author(s):  
Y. X. Wang ◽  
J. T. Crofton ◽  
L. Share

The present study was carried out to investigate whether prostaglandins (PG) are involved in the mechanism that contributes to the sex difference in the antidiuretic and pressor actions of vasopressin. The experiments were performed in conscious male and nonestrous female rats. In hydrated rats, the graded infusion of vasopressin (10-1,000 pg.min 1.kg body wt-1) resulted in a dose-dependent antidiuresis: decreases in urine flow and free water clearance and an increase in urine osmolality. These responses were significantly greater in male than in nonestrous female rats. Pretreatment with a cyclooxygenase inhibitor, indomethacin (10 mg/kg body wt iv), significantly enhanced the antidiuretic response to vasopressin in both sexes. However, the magnitude of this enhancement was greater in female than in male rats. Thus indomethacin abolished the sex difference in the antidiuretic response to vasopressin. In a separate experiment in rats without water hydration and urine collection, infusion of pressor doses of vasopressin (1,000-6,000 pg.min-1.kg body wt-1) resulted in a greater increase in blood pressure in male than in nonestrous female rats. Treatment with indomethacin enhanced this response equivalently in both sexes and thus did not affect the sex difference in the pressor action of vasopressin. These data indicate that renal PG may mediate, at least in part, the sex difference in the antidiuretic action of vasopressin, whereas vascular PG seem not to play an important role in the sex difference in the pressor action of vasopressin.

1999 ◽  
Vol 91 (5) ◽  
pp. 1447-1447 ◽  
Author(s):  
Astrid Chiari ◽  
Joseph R. Tobin ◽  
Hui-Lin Pan ◽  
David D. Hood ◽  
James C. Eisenach

Background Cholinergic agents produce analgesia after systemic and intrathecal administration. A retrospective review showed that intrathecal neostigmine was more potent in women than in men, suggesting a sex difference in this response. The purpose of this study was to determine whether such a sex difference exists in normal rats and to examine the pharmacologic mechanisms that underlie this difference. Methods Male and female rats with indwelling intrathecal catheters received injections of neostigmine, bethanechol (muscarinic agonist), or RJR-2403 (neuronal nicotinic agonist) alone or with atropine (muscarinic antagonist), mecamylamine (nicotinic antagonist), or phentolamine alpha-adrenergic antagonist) with antinociception determined to a noxious heat stimulus to the hind paw. Time versus subcutaneous paw temperature relationships were defined for males and females. Results Neostigmine produced dose-dependent antinociception with five times greater potency in female than in male rats. Neostigmine-induced antinociception was reversed in male rats by atropine and unaffected by mecamylamine, whereas it was partially reduced by each antagonist alone in females and completely reversed after injection of both. RJR-2403 was more potent in females than in males, whereas there was no sex difference to bethanechol. Phentolamine partially reversed antinociception from RJR-2403 in females. Paw temperature increased more rapidly in females than in males for the same lamp intensity. Conclusions These data demonstrate a large sex difference in antinociception to intrathecal neostigmine that is primarily the result of a nicotinic component in females. Phentolamine reversal suggests that part of this nicotinic component may rely on spinal norepinephrine release. A better understanding of this sex difference could lead to development of novel pain therapy for women.


PEDIATRICS ◽  
1970 ◽  
Vol 45 (2) ◽  
pp. 246-253
Author(s):  
H. L. Vallet ◽  
M. Prasad ◽  
Richard B. Goldbloom

Oral chlorpropamide therapy was assessed in 10 children with pitressin-sensitive diabetes insipidus. A significant increase in urine osmolality occurred in eight of nine children studied pre- and post-treatment, with concomitant reduction in urine output and free water clearance. Mean 24-hour urine output during control periods was 5,410 ml (range, 3,000 to 12,000 ml). On chlorpropamide therapy, mean output fell to 2,790 ml (range, 1,200 to 5,500 ml). Complete withdrawal of intramuscular pitressin therapy was possible in 9 of the 10 patients, and these children have now been maintained on chlorpropamide alone for periods of up to 12 months. The principal complication of therapy was symptomatic hypoglycemia, which occurred in half the patients studied during the early phases of treatment. However, it was possible to eliminate this problem by reducing the dose of chlorpropamide while retaining sufficient antidiuretic effect to permit reasonable control of water balance. Current evidence suggests that the antidiuretic action of chlorpropamide may be due to enhancement of the sensitivity of the renal tubule to small amounts of vasopressin. For many, though not all, children with pitressin-sensitive diabetes insipidus, chlorpropamide is a fairly effective therapeutic agent. It is readily accepted by the patients in preference to frequent intramuscular injections of pitressin.


1961 ◽  
Vol 200 (2) ◽  
pp. 400-404 ◽  
Author(s):  
Joseph H. Perlmutt

Conventional clearance techniques were used to study the renal response to vasopressin (5–100 mu/hr.) infused for 2 1/2 hours into anesthetized (pentobarbital), surgically traumatized dogs elaborating a dilute urine. Decreased urine flow, a concomitant sustained increase in Na+ excretion, increased urine osmolality, negative free-water clearance and an increased osmolal U/P ratio (>1, <2) consistently occurred during the infusion of 50 mu/hr. Urinary pH rose and HCO3–, rather than Cl–, was the predominant anion excreted. Tubular rejection of HCO3–, however, is not essential for vasopressin activity under the conditions of this investigation since antidiuresis occurred in an acidotic dog. Usually some increase in glomerular filtration rate and effective renal plasma flow were apparent during vasopressin infusion; the former change could account for the increased Na+ excretion, but it is difficult to ascribe the peculiar anion behavior to this factor. Maximum urinary concentration was not attained even with 100 mu vasopressin/hr.


2002 ◽  
Vol 282 (4) ◽  
pp. R1149-R1155 ◽  
Author(s):  
Jens Lundbæk Andersen ◽  
Niels C. F. Sandgaard ◽  
Peter Bie

The responses to infusion of nitric oxide synthase substrate (l-arginine 3 mg · kg−1 · min−1) and to slow volume expansion (saline 35 ml/kg for 90 min) alone and in combination were investigated in separate experiments. l-Arginine left blood pressure and plasma ANG II unaffected but decreased heart rate (6 ± 2 beats/min) and urine osmolality, increased glomerular filtration rate (GFR) transiently, and caused sustained increases in sodium excretion (fourfold) and urine flow (0.2 ± 0.0 to 0.7 ± 0.1 ml/min). Volume expansion increased arterial blood pressure (102 ± 3 to 114 ± 3 mmHg), elevated GFR persistently by 24%, and enhanced sodium excretion to a peak of 251 ± 31 μmol/min, together with marked increases in urine flow, osmolar and free water clearances, whereas plasma ANG II decreased (8.1 ± 1.7 to 1.6 ± 0.3 pg/ml). Combined volume expansion and l-arginine infusion tended to increase arterial blood pressure and increased GFR by 31%, whereas peak sodium excretion was enhanced to 335 ± 23 μmol/min at plasma ANG II levels of 3.0 ± 1.1 pg/ml; urine flow and osmolar clearance were increased at constant free water clearance. In conclusion, l-arginine 1) increases sodium excretion, 2) decreases basal urine osmolality, 3) exaggerates the natriuretic response to volume expansion by an average of 50% without persistent changes in GFR, and 4) abolishes the increase in free water clearance normally occurring during volume expansion. Thus l-arginine is a natriuretic substance compatible with a role of nitric oxide in sodium homeostasis, possibly by offsetting/shifting the renal response to sodium excess.


1994 ◽  
Vol 267 (2) ◽  
pp. R536-R541 ◽  
Author(s):  
Y. X. Wang ◽  
J. T. Crofton ◽  
H. Liu ◽  
D. P. Brooks ◽  
L. Share

The present study examined whether the antidiuretic response to vasopressin is affected by the estrous cycle and by gonadectomy in conscious, chronically instrumented hydrated rats. Infusion of vasopressin (10-100 pg.min-1.kg body wt-1) resulted in a dose-dependent antidiuresis. Urine volume and free water clearance decreased and urinary osmolality increased with no significant changes in mean arterial blood pressure, heart rate, osmolar clearance, and urinary sodium and potassium excretion. The antidiuretic response to vasopressin was significantly greater in intact male and estrous female rats than in intact female rats in the other phases of the estrous cycle. Thus the calculated doses of vasopressin to reduce urine flow and free water clearance, as well as to increase urinary osmolality 50% from their control values, were significantly higher in nonestrous females than in males and estrous females. Gonadectomy was without effect on the antidiuretic potency of vasopressin in males, but in gonadectomized females the antidiuretic response to vasopressin was enhanced to a level similar to that observed in intact males. These data indicate that the antidiuretic activity of vasopressin is affected not only by gender but also by phase of the estrous cycle and that the ovarian hormone(s) may modulate the antidiuretic action of vasopressin.


2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Alian Désiré Afagnigni ◽  
Maximilienne Ascension Nyegue ◽  
Chantal Florentine Ndoye Foe ◽  
Youchahou Njankouo Ndam ◽  
Frédéric Nico Njayou ◽  
...  

The present work was undertaken to evaluate antidiarrheal activity of ethanolic leaf extract of Dissotis multiflora (Sm) Triana (D. multiflora) on Shigella flexneri-induced diarrhea in Wistar rats and its subacute toxicity. Diarrhea was induced by oral administration of 1.2 × 109 cells/mL S. flexneri to rats. Antidiarrheal activity was investigated in rats with the doses of 111.42 mg/kg, 222.84 mg/kg, and 445.68 mg/kg. The level of biochemical parameters was assessed and organs histology examined by 14 days’ subacute toxicity. S. flexneri stool load decreased significantly in dose-dependent manner. The level of ALT increased (p<0.05) in male rats treated with the dose of 445.68 mg/kg while creatinine level increased in rats treated with both doses. In female rats, a significant decrease (p<0.05) of the level of AST and creatinine was noted in rats treated with the dose of 222.84 mg/kg of D. multiflora. Histological exams of kidney and liver of treated rats showed architectural modifications at the dose of 445.68 mg/kg. This finding suggests that D. multiflora leaf extract is efficient against diarrhea caused by S. flexneri but the treatment with doses lower than 222.84 mg/kg is recommended while further study is required to define the exact efficient nontoxic dose.


2015 ◽  
Vol 3 (1) ◽  
pp. 5 ◽  
Author(s):  
Barnabé Lucien Nkono Ya Nkono ◽  
Selestin Dongmo Sokeng ◽  
Paul Désiré Dzeufiet Djomeni ◽  
Frida Longo ◽  
Pierre Kamtchouing

<p><strong>Methodology:</strong> Wistar rats were randomly assigned into eight groups of five animals each: four male groups and four female groups. Each sex group had a control group receiving distilled water and three test groups receiving 200, 500 and 1000mg/kg respectively. Animal’s body weights were recorded on the first day and once a week for the four experiment weeks. The hematological analysis included total WBC count, total RBC count, Hb, %HCT, MCV, MCH and MCHC. Biochemical/serum profile studies include TG, TC, ALT, AST, urea and TP. Tissue specimens of the liver, kidney and lung were subjected to histological examination using standard hematoxylin-eosin staining.</p><p><strong>Results:</strong> In male rats, aqueous extract showed significant decreases in relative weight of liver with extreme significance P&lt;0.001 at a dose of 200mg/kg (vs. control group), P&lt;0.001 of lung at all the doses, P&lt;0.05 (200 and 500mg/kg) and P&lt;0.01 (1000mg/kg) in heart weight. In relative kidney weight, only the dose of 1000mg/kg showed a significant increase vs. normal control male rats. Unlike male rats, only relative kidney weight in female rats was significantly different from the control group in a dose-dependent manner. The aqueous extract treated male groups showed significant increases P&lt;0.001 (1000mg/kg) of total WBC count and MCHC, significant decreases of %HTC (dose response manner), P&lt;0.05 total RBC count (at doses of 500 and 1000mg/kg) and Hb P&lt;0.01 (500mg/kg) vs. normal male rats. In female rats, the haematological study showed significant increase P&lt;0.01 of total WBC count (at the doses of 500 and 1000mg/kg), significant decreases P&lt;0.05 and P&lt;0.01 of total RBC respectively at the doses of 200 and 1000mg/kg, significant decrease of Hb with extreme significance P&lt;0.001 at the dose 1000mg/kg, %HTC also decrease dose response manner vs. control female rats. Biochemical study showed in male rats significant decreases in level of TG P&lt;0.001 (at the doses of 200 and 500mg/kg) and urea, although it showed any dose-dependent effect vs. control male rats. AST also decreases (P&lt;0.05) in male rats at the dose of 200mg/kg but significantly increase P&lt;0.001 at the dose of 500mg/kg. In the female rats, biochemical study revealed significant increases in level of TG P&lt;0.001 and urea P&lt;0.01 at the dose of 200mg/kg and significant decreases in level of TG P&lt;0.01, AST P&lt;0.05 and urea P&lt;0.05 at the dose of 500mg/kg (vs. control female rats). Microscopically, there were mild hepatic and renal tissue injuries supporting the hematological analysis.</p><p><strong>Conclusion:</strong> The results indicated that aqueous extract of <em>Alstonia boonei</em> De Wild is toxic in high doses.</p>


1977 ◽  
Vol 232 (4) ◽  
pp. F335-F340 ◽  
Author(s):  
J. D. Wallin ◽  
R. A. Kaplan

Mechanisms for the concentrating defect produced by fluoride were examined in the rat. Free-water clearance at all levels of delivery was normal after 5 days of chronic fluoride administration in the hereditary hypothalamic diabetes insipidus rat. In the Sprague-Dawley rats, during moderate fluoride administration (120 micronmol/kg per day), urine osmolality and cyclic AMP excretion decreased and urine volume increased, but after exogenous vasopressin, volume decreased and osmolality and cyclic AMP increased appropriately. During larger daily doses of fluoride (240 micronmol/kg per day) urinary osmolality and cyclic AMP decreased and volume increased, which was similar to the changes seen during lower fluoride dosages, but these parameters did not change after exogenous vasopressin. These data suggest that ascending limb chloride reabsorption is unaltered by fluoride administration; in the presence of sufficient fluoride, collecting tubular cells apparently do not generate cyclic AMP or increase permeability appropriately in response to vasopressin. The postulated defect is felt to be due to either a decrease in ATP availability or to a direct inhibitory effect of fluoride on the vasopressin-dependent cyclic AMP generating system.


1988 ◽  
Vol 254 (4) ◽  
pp. R641-R647 ◽  
Author(s):  
T. J. Vokes ◽  
N. M. Weiss ◽  
J. Schreiber ◽  
M. B. Gaskill ◽  
G. L. Robertson

Changes in osmoregulation during normal menstrual cycle were examined in 15 healthy women. In 10 women, studied repetitively during two consecutive menstrual cycles, basal plasma osmolality, sodium, and urea decreased by 4 mosmol/kg, 2 meq/l, and 0.5 mM, respectively (all P less than 0.02) from the follicular to luteal phase. Plasma vasopressin, protein, hematocrit, mean arterial pressure, and body weight did not change. In five other women, diluting capacity and osmotic control of thirst and vasopressin release were assessed in follicular, ovulatory, and luteal phases. Responses of thirst and/or plasma vasopressin, urine osmolality, osmolal and free water clearance to water loading, and infusion of hypertonic saline were normal and similar in the three phases. However, the plasma osmolality at which plasma vasopressin and urine osmolality were maximally suppressed as well as calculated osmotic thresholds for thirst and vasopressin release were lower by 5 mosmol/kg in the luteal than in the follicular phase. This lowering of osmotic thresholds for thirst and vasopressin release, which occurs in the luteal phase, is qualitatively similar to that observed in pregnancy and should be taken into account when studying water balance and regulation of vasopressin secretion in healthy cycling women.


2021 ◽  
Vol 19 (4) ◽  
Author(s):  
О.А. Olenovych

The aim of the study – to explore the role of the renin-angiotensin-aldosteronesystem (RAAS) in the disturbance of ionoregulatory renal function in alloxan-inducedexperimental diabetes mellitus (EDM).Material and methods. The experiments were carried out on 78 white non-linearmature male rats with 11-, 26- and 46-day long alloxan-induced EDM with underlyingpharmacological blockade of RAAS by administration of kaptopril. The study ofionoregulating function of the kidneys was provided by the clearance method under thecondition of water 2-hour diuresis.Results. Pharmacological blockade of RAAS in rats with alloxan-induced EDM causedan intensification of natriuresis at all stages of the experiment: increased urinaryconcentration of sodium ions, its excretion and clearance. On the 11th day of EDM, thesodium filtration charge increased with the development of hyponatremia, proximal anddistal sodium reabsorption standardized in volume of glomerular filtrate (GF) decreased,kaliuresis was suppressed, and sodium-free water clearance elevated. In case of 26-daylong EDM, the sodium filtration charge decreased, its absolute and relative reabsorption,the distal sodium reabsorption standardized by GF increased. Kaliuresis increased. In46-day long EDM, the sodium filtration charge decreased, and hyponatremia enhanced.Absolute and relative sodium reabsorption reduced due to both – proximal and distal.Kaliuresis augmented, the clearance of sodium-free water declined.Conclusions. The increase in urinary sodium loss during the 11-day EDM is stipulatedby glomerular hyperfiltration, causing a functional weakening of the tubulotubularbalance and relative dysfunction of the distal segment of the nephron, emphasizing therenoprotective effect of RAAS on ionoregulatory function of the kidneys. The decrease inthe total reabsorption potential of the tubular segment of the nephron in the dynamics ofEDM development reflects on the proximal tubules, and preserved tubulotubular balancecertifies functional intactness of the distal tubules in 26-day long EDM. RAAS pathologicalactivation and attenuation of the renal blood flow autoregulation by tubuloglomerularfeedback may serve as an initiating factor in the development of tubular disorders in 26-day long alloxan diabetes with following progression in 46-day long EDM.


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