Hypertensive mechanisms and converting enzyme inhibitors.
The introduction of angiotensin-converting enzyme (ACE) inhibitors marks a new era in the understanding and treatment of high blood pressure. Although the benefits of therapy with ACE inhibitors are documented, it is more difficult to isolate the principal mechanisms that account for their effective actions in the treatment of hypertension. Recent data suggest that these agents affect both the pressor and depressor mechanisms that regulate vascular tone and cardiac function. For example, ACE inhibitors decrease angiotensin II-mediated vasoconstriction, reduce adrenal medullary catecholamine release, restore baroreceptor activity, and normalize vasomotor sympathetic activity. Experimental work indicates that ACE inhibitors also act on hypertensive mechanisms via actions on the central nervous system. Cardiovascular centers in the brain have receptor sites for angiotensin II and contain the proteins required for local synthesis of angiotensins. Vasomotor neurons possess such receptors and exhibit ACE activity. In addition, angiotensin II receptors involved in the regulation of baroreceptor activity are present in neuronal elements of the baroreflex arc. It is suggested that ACE inhibitors reach the brain via circumventricular organs to reduce sympathetic activity and enhance baroreceptor sensitivity. New studies suggest that depressor actions of ACE inhibitors include enhanced biosynthesis of vasodilator prostaglandins. From animal experiments it is deduced that enhanced production of angiotensin-(1-7) after inhibition of ACE stimulates release of vasodilator prostaglandins. These investigations clarify the function of tissue renin-angiotensin systems in the control of blood pressure in both normal and hypertensive states.
Ferrario
C M
CM
Department of Brain and Vascular Research, Cleveland Clinic Foundation, Ohio 44195.
Jaiswal
N
N
Yamamoto
K
K
Diz
D I
DI
Schiavone
M T
MT
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D012084:Renin-Angiotensin System / Q000187:drug effects* / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors