Multifactorial analysis of chronic hypertension induced by electrolyte-active steroids in trained, unanesthetized dogs.
Chronic hypertension has been produced in mongrel dogs by the long-term oral administration of metyrapone (100 mg/kg per day). This model is characterized hemodynamically by wide variations in cardiac output and extracellular fluid volume and metabolically, by hypokalemia, suppressed plasma renin activity, and elevated plasma deoxycorticosterone values. Unlike the deoxycorticosterone acetate (DOCA)-saline hypertensive rat, it is associated with decreases rather than increases in plasma catecholamines. Reasons for the raised arterial pressure induced by metyrapone were sought (1) by exploring the role of cardiac output in the initiation and maintenance of hypertension, (2) by an assessment of neural contribution through the study of circulating catecholamines and use of adrenergic blocking drugs, and (3) by determining its relation to dietary sodium. The rise in pressure was not uniformly associated with an increase in cardiac output nor did prevention of rises in output by beta-blockade prevent the development of hypertension. Similarly, pretreatment with either centrally acting (clonidine) or peripherally acting (guanethidine) adrenergic blocking drugs failed to prevent the hypertension or change its pattern. In contrast, salt deprivation was singularly effective in preventing the rise in arterial pressure while increased salt intake led to parallel elevations in both blood pressure and peripheral resistance. These results point to a primary role of arteriolar resistance in determining the initiation and maintenance of hypertension induced by electrolyte-active steroids. In this regard, they agree with other reports of early changes in both membrane and structural properties of vascular smooth muscle that antedate the rise in pressure induced by DOCA and 1% saline.
D000070:Acebutolol / Q000008:administration & dosage; D000450:Aldosterone / Q000097:blood; D000818:Animals; D002908:Chronic Disease; D003000:Clonidine / Q000008:administration & dosage; D003345:Corticosterone / Q000097:blood; D004039:Diet, Sodium-Restricted; D004195:Disease Models, Animal; D004285:Dogs; D006145:Guanethidine / Q000008:administration & dosage; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000139:chemically induced*; D008297:Male; D008797:Metyrapone / Q000008:administration & dosage / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D011292:Premedication; D012083:Renin / Q000097:blood
D000450:Aldosterone; D000070:Acebutolol; D012083:Renin; D003000:Clonidine; D003345:Corticosterone; D009638:Norepinephrine; D008797:Metyrapone; D006145:Guanethidine