Effects of Chronic Administration of Angiotensin Converting Enzyme (ACE) Inhibitors on Blood Pressure and Tissue ACE Activity in the SHR

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Abstract
Although ACE inhibitors have proven clinically effective as antihypertensive agents, the mechanisms by which they lower blood pressure are not clearly understood. While inhibition of circulating enzyme has been thought to be of primary importance, reductions in circulating angiotensin II levels do not appear to mediate the antihypertensive effects of ACE inhibitors in hypertensive animals or man (1,2). As previously demonstrated, inhibition of tissue components of the renin-angiotensin system may be an important factor involved in blood pressure reduction (1,3). In this regard, we have shown in a comparative study of several ACE inhibitors that while inhibition of circulating ACE activity is not well correlated with antihypertensive effects in SHR, changes in aorta and/or brain may be necessary for the acute effects of these compounds (4). In the present study, we have compared the chronic effects of enalapril and two new ACE inhibitors, CGS 14824A and CGS 16617, on blood pressure, tissue ACE activity, and components of the renin-angiotensin system in conscious SHR. CGS 14824A, like enalapril, is an ester pro-drug, while CGS 16617 is a diacid which does not require hydrolysis for in vivo activity.