It is well known that the prevalence of hypertension is less in premenopausal women than in men of the same age. In addition, women develop less severe levels of hypertension than men. Although the reason for these sex differences is unknown, it has been proposed that estrogen may protect against hypertension, while testosterone may exaggerate the development of hypertension. The overall objective of this proposal is to determine if there are sex differences in renal function in rats genetically predisposed to hypertension. The hypothesis to be tested is that sex hormones alter renal sodium and water handling such that female rats more efficiently excrete sodium and water than male rats, thus delaying and/or attenuating the development of salt-induced hypertension in females. The proposed studies will be conducted in prehypertensive male and female Dahl salt-sensitive (S) and Dahl salt-resistent (R) rats. These animals will be studied in the intact state, after gonadectomy, and after gonadectomy with sex hormone replacement.
Specific Aim #1 is to compare the effects of removal and replacement of estrogen and testosterone on glomerular filtration rate and renal blood flow in normotensive Dahl S and R rats during basal conditions and in response to renal nerve stimulation and administration of phenylephrine, guanabenz and angiotensin II. It is expected that the hemodynamic and tubular responses to circulating vasoconstrictors and renal nerve stimulation will be attenuated in females as compared male rats.
Specific Aim #2 is to compare the effects of removal and replacement of estrogen and testosterone on pressure natriuresis and diuresis in normotensive Dahl S and R rats. These experiments will determine if male Dahl S rats have an exaggerated blunting of the pressure natriuresis and diuresis curves as compared to females.
Specific Aim #3 is to compare the effect of removal and replacement of estrogen and testosterone on the neural control of renal sodium and water excretion in normotensive Dahl S and R rats by examining diuretic, natriuretic and renal sympathetic nerve activity responses to an acute intravenous volume load. It is hypothesized that male Dahl S rats will respond to volume expansion with an attenuated decrease in renal nerve activity and an attenuated sodium and water excretion as compared to female Dahl S rats.
