Role of the renin-angiotensin system in the control of vasopressin and ACTH secretion during the development of renal hypertension in dogs.

Abstract

SUMMARY Experiments were performed to determine if the activation of the renin-angiotensin system that occurs during the development of two-kidney, one clip Goldblatt hypertension in dogs is accompanied by increases in vasopressin and adrenocorticotrophic hormone (ACTH) secretion. Following renal artery constriction, there were marked increases in arterial blood pressure, plasma renin activity (PRA), and plasma angiotensin II (All) concentration. These changes were accompanied by an increase in plasma vasopressin concentration during the second week following constriction, and there were significant correlations between plasma vasopressin concentration and PRA (r = 0.57, p < 0. T HE activity of the renin-angiotensin system is increased in a variety of forms of experimental and human hypertension.' • 2 Administration of agents that block the formation or actions of angiotensin II (All) lowers blood pressure in these hypertensive states, indicating that the hypertension is dependent, at least in part, on the renin-angiotensin system. 1 -2The hypertensive action of All is largely the result of its direct action to constrict vascular smooth muscle. However, All may also influence arterial pressure by a number of indirect mechanisms. For example, it is known to stimulate the secretion of vasopressin and adrenocorticotrophic hormone (ACTH), 3 " 5 two peptides that can have marked effects on blood pressure. 6 -7 It is therefore possible that the elevated All levels in some hypertensive states increase the secretion of va- sopressin and ACTH, which in turn act to increase blood pressure. Moreover, it is possible that the antihypertensive effect of blockade of the renin-angiotensin system is partly due to inhibition of the stimulatory action of All on vasopressin and ACTH secretion.The present experiments were designed to test these possibilities. This was accomplished by monitoring the plasma levels of renin, All, vasopressin, and corticosteroids (used as an index of ACTH secretion) during the development of two-kidney, one clip Goldblatt hypertension in dogs. In addition, the effect of blockade of the renin-angiotensin system with captopril or saralasin on the secretion of these hormones was studied at different times during the development of hypertension. MethodsThe experiments were performed on five mongrel dogs of both sexes, weighing 18-34 kg. They had free access to water and were fed a diet of Purina dry dog chow (Ralston Purina Company, St. Louis, Missouri), which provided approximately 80 mEq sodium/day. Under sodium pentobarbital anesthesia (30 mg/kg,

Effect of angiotensin II on plasma ACTH in patients with Addison's disease

“…In the animal experiments by Ramsay et al (1978), Reid et al (1982) and Rivier & Vale (1983) mentioned earlier, All infusion rates larger than 10 ng/kg/min or large-dose bolus injections of All were required to raise plasma ACTH or corticosteroid levels. In a study by Ben et al (1984) on acute renovascular hypertension in dogs, an in¬ crease of plasma All from about 20 pg/ml to between 60 and 140 pg/ml for several days was not accompanied by a significant change in plasma corticosteroid concentration. Conversely, adminis¬ tration of Captopril to dogs with high plasma All levels failed to change plasma corticosteroids.…”

Norepinephrine kinetics in dogs with experimentally induced renal vascular hypertension

“…4 Results of a number of studies indicate that blockade of the renin-angiotensin system does not normalize blood pressure in dogs with experimentally induced, or in humans with naturally developing, renal vascular hypertension. [5][6][7][8] These findings suggest that other vasopressor systems may participate in the development and maintenance of renal vascular hypertension, especially that induced by use of the 2K2C model.…”

Are hypertensive effects of aldosterone, angiotensin, vasopressin, and norepinephrine chronically additive?

“…16 -2I Infusion rates that raise plasma levels 40 to 60 pg/ml (5.0 ng/kg/min) are required to experimentally produce a sustained 25 to 30 mm Hg elevation of pressure with a normal Na intake. 2122 In moderate essential hypertension, plasma ANG II, plasma renin activity, and ALDO seldom reach levels that exceed twice the normal range.…”