Hemodynamic and neurohormonal changes in the development of DOC hypertension in the dog.
In this article we summarize studies of the hemodynamic and endocrine effects of desoxycorticosterone (DOC)-induced hypertension in dogs and also review new data of the action of this steroid on baroreceptors. The hemodynamic effect of subcutaneous injections of DOC to dogs, without supplementation of salt in their diet, consisted of increases in arterial pressure that were sustained for a 28-day observation period and associated with augmented cardiac output. At the early stage of the hypertensive response there was a rise in plasma Na+ concentration accompanied by increases in the plasma and cerebrospinal fluid (CSF) levels of vasopressin. The activity of the peripheral renin angiotensin system, as evaluated by the longitudinal changes in plasma renin activity and plasma immunoreactive angiotensin II (irAng-II), was markedly depressed in the hypertensive dogs. In contrast, the concentration of irAngII in the CSF did not change. Additional studies of the carotid occlusion reflex in anesthetized dogs revealed an enhanced buffering baroreceptor capacity in the early (less than day 10), but not the late (greater than day 28), stages of the hypertension. The abnormality in baroreflex function may be mediated by an effect of the steroid on an activity of brain angiotensin II that influences the inhibitory interaction between high and low pressure baroreceptors. The data acquired in these studies agree with the notion that excess mineralocorticoid production causes hypertension by mechanisms that influence the neurohormonal control of blood pressure by the central nervous system.
Ferrario
C M
CM
Department of Brain and Vascular Research, Cleveland Clinic Foundation, OH 44106.
Mohara
O
O
Ueno
Y
Y
Brosnihan
K B
KB
D000804:Angiotensin II / Q000097:blood / Q000134:cerebrospinal fluid; D000818:Animals; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004285:Dogs; D006439:Hemodynamics; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D011311:Pressoreceptors / Q000187:drug effects*; D012083:Renin / Q000097:blood; D012964:Sodium / Q000097:blood / Q000134:cerebrospinal fluid; D014667:Vasopressins / Q000097:blood / Q000134:cerebrospinal fluid
D014667:Vasopressins; D000804:Angiotensin II; D003900:Desoxycorticosterone; D012964:Sodium; D012083:Renin