Effect of gender on the antidiuretic activity of vasopressin in the spontaneously hypertensive rat

Ye, Dailin
Uyehara, Catherine FT
Biomedical Sciences (Pharmacology)
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University of Hawaii at Manoa
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Recently, studies have found that circulating vasopressin levels, as well as the cardiovascular and antidiuretic actions of vasopressin are greater in males than in females, but the consequences of these gender differences are unclear. Further, animal and human studies have revealed that hypertension develops more rapidly and is more prevalent in males than in females. Because vasopressin is involved with blood pressure regulation, whether vasopressin gender differences are involved in the gender difference of hypertension development should be examined. Thus, this dissertation tested the hypothesis that a gender effect on vasopressin renal action contributes to gender differences in hypertension. Renal function of male and female adult spontaneously hypertensive rats (SHR) were compared to that of normotensive (WKY) rats. Vasopressin V2 receptors were pharmacologically stimulated with a selective V2 receptor agonist, which revealed that maximal urine concentrating abilities of SHR were higher than that of WKY. While there were significant differences in concentrating abilities with hypertension, there were no significant gender differences in responses to maximal V2 stimulation in normotensive or hypertensive rats. The contribution of endogenous vasopressin on renal fluid handling to a gender difference in hypertension was also examined. Vasopressin inhibition with a selective V2 antagonist resulted in higher free water clearance in females than in males of both strains. Also, the renal response to endogenous vasopressin blockade was lower in SHR than WKY in both sexes. Expression of V2 receptors in renal inner medulla of male SHR and WKY showed that levels of V2 receptor mRNA in SHR were significantly lower than those in WKY. Thus, differences in renal fluid handling abilities between strains and gender, may be due to the differences in endogenous vasopressin levels, renal concentrating abilities, or expression of renal vasopressin receptors. In conclusion, vasopressin influence on renal fluid handling is altered in established hypertension. While there are differences in vasopressin renal action between males and females in both strains, there were no significant differences in the gender effect between normotensive and hypertensive adult rats. Thus, whether gender differences in fluid handling contribute to gender differences in hypertension development remains to be determined.
xvii, 157 leaves
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Theses for the degree of Doctor of Philosophy (University of Hawaii at Manoa). Biomedical Sciences (Pharmacology); no. 4372
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