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SUMMARY Experiments were performed to determine the role of vasopressin in deoxycorticosterone (DOC)-salt hypertension. In order to determine if vasopressin is necessary for the development of DOC-salt hypertension, rats with hereditary diabetes insipidus (DI) and normal Long-Evans rats (LE) were unilaterally nephrectomized, treated with DOC Pivalate (30 mg/kg • week) and given saline to drink for 8 weeks. A second group of DI rats were unilaterally nephrectomized, but received no treatment. Systolic blood pressure (SBP) increased 40 mm Hg in the LE group (p < 0.01) but failed to increase significantly in either DI group. Urinary excretion of vasopressin (U ADH V) and SBP were measured in unilaterally nephrectomized LE rats treated with DOC and salt (DOC-LE), salt alone (NaCI-LE) and untreated rats (H.O-LE). The UADHV was elevated in DOC-LE (j> < 0.01) and NaCI-LE (p < 0.05) rats, but only the DOC-LE rats became hypertensive. Finally, the I.V. injection of analogs of vasopressin, which block its pressor but not antidluretic activity, lowered mean arterial blood pressure 27 ± 5 mm Hg in 11 conscious DOC-salt hypertensive rats. It is concluded that vasopressin plays a major role as a pressor agent in both the onset and maintenance of DOC-salt hypertension.

We have shown previously that, in rats with deoxycorticosterone (DOC)-salt hypertension, arterial blood pressure rises more rapidly and reaches a higher level in male than in female rats and that the course of the hypertension was ameliorated by gonadectomy in male rats and exacerbated by gonadectomy in female rats. The present investigation was undertaken to examine the role of the gonadal steroid hormones in modulating the course of DOC-salt hypertension in the rat. Our previous findings with respect to the effects of gender and gonadectomy on DOC-salt hypertension were confirmed in this study. Chronic treatment with gonadal steroids was begun 1 week before the start of the DOC-salt protocol. 17 beta-Estradiol attenuated the course of the hypertension in intact male rats and in gonadectomized females. Testosterone exacerbated the development of the hypertension in gonadectomized male rats but was without effect in intact females. Progesterone alone had no effect on the hypertension in ovariectomized rats but when given to ovariectomized rats in combination with estradiol transiently prevented the ameliorating effect of the estradiol. These effects of the gonadal steroid hormones could not be attributed to effects of saline intake. Thus, these findings demonstrate that the gonadal steroid hormones play an important role in modulating the pathogenesis of DOC-salt hypertension in the rat. It is suggested that the effects of the gonadal hormones on the course of the hypertension may be due to modulation of the cardiovascular and renal actions of vasopressin, since vasopressin is required for this model of hypertension.

SUMMARY To investigate a possible sex difference in the development of deoxycorticosterone (DOC)-salt hypertension in rats, systolic blood pressure was measured over 6 weeks in unilaterally nephrectomized male and female rats with or without DOC-salt treatment. Throughout the treatment, systolic blood pressure was significantly lower in female than in male DOC-salt rats (at the end of the sixth week: 190 ± 8 vs 163 ± 7 nun Hg, p < 0.05). The difference in blood pressure was also confirmed by the direct measurement of mean arterial pressure at the end of the experiment. The 24-hour urinary excretion of vasopressin was significantly higher in male control rats than in female control rats; however, no difference was observed between male and female DOC-salt rats, in which the urinary excretion of vasopressin was four to five times higher than in control rats. The plasma vasopressin concentration was higher in DOC-salt rats, but there were no differences between sexes. These were no differences in the metabolic clearance rate of vasopressin among the four groups of rats. This indicates that the elevated plasma vasopressin concentration in DOC-salt hypertensive rats is due to increased release of the hormone, rather than to impaired metabolism. Thus, although vasopressin plays a pivotal role in the pathogenesis of DOC-salt hypertension, the sexual dimorphism in this form of hypertension cannot be attributed to differences in the secretion, metabolism, or plasma concentration of vasopressin. (Hypertension 9: 172-177, 1987) KEY WORDS • deoxycorticosterone-salt hypertension metabolic clearance rate sex difference • vasopressin T HE lower incidence of hypertension in women before menopause than in men is an established epidemiological observation. 12 It has also been reported that in some genetic models of hypertension, such as spontaneously hypertensive rats 3 -4 and Dahl salt-sensitive rats, 5 the female is less hypertensive than the male rat. The mechanisms responsible for this sex difference have not been elucidated, but involvement of the gonadal hormones seems likely, since gonadectomy and treatment with gonadal steroids can influence the course of the hypertension in these genetic models.3 " 7In the present study, we investigated the question of whether there is sexual dimorphism in the develop- Received May 19, 1986; accepted August 19, 1986. ment of deoxycorticosterone (DOC)-salt hypertension in the rat. This issue has not, to our knowledge, been systematically investigated. Furthermore, since vasopressin is a prerequisite for the development and maintenance of this form of hypertension, 8 " 10 and since recent evidence" indicates that vasopressin secretion is higher in normotensive male than in female rats, experiments also were designed to determine whether any differences in the development of DOC-salt hypertension between male and female rats are accompanied by differences in the rate of secretion or metabolism of vasopressin. Materials and Methods Experiment 1Twenty male and 20 female 5-week-old Sp...

Previously, we reported that, in the rat, pressor responsiveness to vasopressin (VP) is higher in males than in females during most phases of the estrous cycle. To explore the role of the vasculature in this phenomenon, we examined vascular reactivity to VP in thoracic aortas of male rats and female rats during each phase of the estrous cycle. Aortic rings were prepared from age-matched male and female Sprague-Dawley rats and mounted for isometric tension recording. Maximal response of female aortas to VP (4,246 +/- 163 mg/mg ring dry wt) was more than twice (P less than 0.001) that of male aortas (1,877 +/- 215 mg/mg ring wt). Sensitivity of female aortas to VP was substantially higher (P less than 0.001) than that of male aortas (EC50: 10.9 +/- 0.7 vs. 19.0 +/- 1.6 nM, respectively). Maximal rate of tension development (dT/dtmax) during contraction with VP was nearly twofold higher (P less than 0.01) in female aortas (536 +/- 23 mg/min) than in male aortas (300 +/- 19 mg/min). Maximal response, sensitivity, and dT/dtmax of female aortas did not vary significantly during the estrous cycle. Maximal response of female aortas to phenylephrine (PE; 1,251 +/- 93 mg/mg ring wt) was half that (P less than 0.001) of male aortas (2,546 +/- 194 mg/mg ring wt); sensitivity to PE did not differ significantly (EC50: 0.33 +/- 0.02 vs. 0.38 +/- 0.06 microM, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)