Abstract. Adult male and female spontaneously hypertensive rats (SHR-Okamoto, Kyoto) were gonadectomized when they were 17 weeks old. Intact SHR showed a progressive increase of their blood pressure with growth, attaining systolic pressure levels of 194–208 in males and 163–173 mmHg in females when they were 29–30 weeks old. During this same period, the gonadectomized animals showed a significant reduction in blood pressure ranging from 168–175 in males and from 158–163 mmHg in females. These studies indicate that male and female SHR gonadectomized at 17 weeks of age do not show the progressive blood pressure rise that occurs in intact SHR. There was no change in heart rate in either sex. Corticosterone (B) levels in plasma were increased in the orchidectomized males, and 18-OH-DOC levels in plasma were increased in the adrenal glands of ovariectomized females indicating that these hormonal changes probably do not play a role in SHR hypertension. It appears that gonadal and other hormones are involved in the pathogenesis of SHR hypertension.

Adrenergic regulation of adenylate cyclase activities in the zona glomerulosa (the capsular fraction) and the zona fasciculata-reticularis (the decapsulated fraction) from rat adrenocortical glands has been investigated. Specific binding of [3H]dihydroalprenolol to the membrane from the capsular and the decapsulated fractions was saturable with dissociation constant (Kd) of 4.67 and 5.1 microM, respectively. The receptor density in the capsular and the decapsulated fractions was 230 and 235 fmol/mg protein, respectively. The potencies which isoproterenol, epinephrine, salbutamol, and norepinephrine competed with [3H]dihydroalprenolol binding sites indicted that adrenergic receptors of the capsular and the decapsulated membranes were of the beta 2-type. beta-Adrenergic stimulation of the adenylate cyclase system was observed only in the capsular fraction. This suggests that beta-adrenergic receptors of the capsular membrane are associated with their adenylate cyclase system, but those of the decapsulated membrane are not. Maximum stimulatory concentrations of ACTH and isoproterenol had no additive effect on the capsular adenylate cyclase, indicating that receptors for ACTH and beta-adrenergic agonists are coupled to a common pool of the cyclase.

Pregnant women with hyperinsulinemia are at increased risk of developing gestational hypertension.

Effects of angiotensin II on corticoid biogenesis and cAMP levels in the zona fasciculata-reticularis (the decapsulated fraction) and the zona glomerulosa (the capsular fraction) from the rat adrenal gland have been studied. Angiotensin II exclusively stimulated steroidogenesis in the zona glomerulosa without stimulation of the cAMP system, suggesting that steroidogenic action of this polypeptide does not involve the adenylate cyclase system. Angiotensin II was also found to stimulate cAMP-phosphodiesterase activity in the zona glomerulosa. An elevation of calcium concentration in the incubation medium has been observed to be effective in stimulating the production of aldosterone and cAMP by the capsular fraction. Angiotensin II caused a significant enhancement of the steroidogenic response of the capsular fraction to increasing calcium concentration regardless of the response of the cAMP system to calcium. This steroidogenic effect of angiotensin II was completely abolished by calcium antagonists added to the incubation medium without any inhibitory effect on the calcium-induced accumulation of tissue cAMP. These results suggest that angiotensin II acts on the adrenal II acts on the adrenal glomerulosa cell to increase intracellular calcium, which in turn directly stimulates steroidogenesis concomitant with the increased activity of phosphodiesterase.

Effects of ACTH and calcium on cyclic AMP and steroid production by the zona fasciculata-reticularis (the decapsulated fraction) from the rat adrenal cortex have been studied. Increasing concentrations of extracellular calcium enhanced the action of ACTH on cyclic AMP and steroid production. These effects of ACTH with calcium were prevented by lanthanum, but not by tetracaine or verapamil, suggesting that ACTH stimulation may be mediated by calcium through a process not involving the tetracaine- or verapamil-vulnerable step(s) of the calcium current. High concentrations of external calcium itself increased cyclic AMP accumulation without any increase in steroidogenesis. A calcium ionophore, X537A was stimulatory for steroidogenesis but inhibitory with respect to cyclic AMP accumulation. Considered together with the findings of steroidogenic stimulation by low concentrations of ACTH without cyclic AMP increase, these results suggest that ACTH primarily increases intracellular calcium mobilization thus stimulating directly the steroidogenesis, which is independent of the cyclic AMP system. Relatively high concentrations of ACTH activate the adenylate cyclase, which depends on extracellular calcium to increase cyclic AMP levels and stimulation of steroidogenesis by the decapsulated fractions of the adrenal cortex.