Angiotensin converting enzyme inhibitors. Present and future.
The angiotensin converting enzyme (ACE)-inhibiting agents have emerged with the diuretic agents, beta-adrenergic receptor-blocking agents, and calcium antagonists as therapeutic options for major consideration during the initial treatment of hypertensive patients. These compounds antagonize a potent pressor mechanism underlying hypertensive disease. The ACE inhibitors curtail the generation of the potent octapeptide angiotensin II; in addition, degradation of the potent vasodilator bradykinin is inhibited. Hemodynamically, ACE inhibitors reduce arterial pressure through a decreased total peripheral resistance that is unassociated with reflex stimulation of the heart or expansion of intravascular volume. The arteriolar dilation accounting for the decreased vascular resistance seems to occur in each target organ of the disease. Unlike the direct-acting smooth muscle vasodilators or adrenergic inhibitors, ACE inhibitors dilate the efferent as well as the afferent glomerular arterioles and thereby reduce glomerular hydrostatic pressure and renal filtration fraction, even though renal blood flow and glomerular filtration rate are preserved. The ACE-inhibiting compounds not only reduce left ventricular afterload in hypertension but also diminish cardiac mass and wall thicknesses. The mechanism(s) for some of these actions have not yet been defined precisely, but they undoubtedly involve the autocrine/paracrine actions of the renopressor system and their effects in the cellular biologic events of vascular smooth muscle and the cardiac myocyte. It seems plausible and exciting that the "more local" renin-angiotensin systems will be exploited by those ACE inhibitors yet to be synthesized, which will result in new applications for this class of pharmacological agents.
Frohlich
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Office of the Vice President for Academic Affairs, Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121.
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D005544:Forecasting; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D012084:Renin-Angiotensin System / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors