Characteristics of hormonal and neurogenic mechanisms of deoxycorticosterone-induced hypertension

Abstract

We characterized the hemodynamk and endocrine changes associated with the evolution of steroid-induced hypertension in conscious, trained, instrumented dogs given intramuscular injections of deoxycorticosterone (DOC) pivalate on Days 1 (20 mg/kg) and 14 (10 mg/kg) of the study. Because hypertension could be produced in these dogs without salt loading and unilateral nephrectomy, the research afforded a novel opportunity to determine the primary effects of DOC excess on the renin-angiotensin and sympathetic nervous systems, and on vasopressin levels. Both before and during 28 days of DOC treatment, regular measurements of mean arterial pressure, heart rate, cardiac output, and total peripheral resistance were coupled with serial determinations of plasma and cerebrospinal fluid levels of angiotensin II, vasopressin, norepinephrine, and electrolytes. DOC induced a progressive rise in mean arterial pressure associated with increased cardiac output and no change in heart rate. These hemodynaqiic changes were accompanied by sustained decreases in plasma renin activity, and in plasma, but not cerebrospinal fluid, angiotensin II. In contrast, plasma and cerebrospinal fluid vasopressin rose transiently on the 7th and 14th days of the study, respectively. After anesthesia with morphine and chloralose, the hemodynamic response to occlusion of a sole innervated carotid artery was evaluated on the 5th week before and after cervical vagotomy. Compared to normal unimals, dogs with DOC-induced hypertension showed a reduced pressor response to carotid occlusion associated with suppression of reflex tachycardia; vagotomy partially restored the pressor response to normal levels. The data suggest that DOC-induced hypertension changes central hormonal influences of cardiovascular function, and also alters cardiopulmonary baroreceptor reflex control of peripheral sympathetic nerve activity. © 1988 American Heart Association, Inc.