Increases in cardiac kinins as a new mechanism to protect the heart.

Numerous workers have documented that angiotensin-converting enzyme (ACE) inhibitors have antihypertensive and antihypertrophic effects, which in most cases are attributed to decreased angiotensin II (Ang II). However, reports ascribing some of the cardiovascular effects of ACE inhibitors to kinin potentiation have been published for a number of years. In an article in the present issue of Hypertension, Gohlke et al used an experimental model of genetic hypertension, the stroke-prone spontaneously hypertensive rat (SHRSP), to study whether long-term treatment with low, non-antihypertensive doses of an ACE inhibitor (ramipril) might have an effect on cardiac function that is dependent on kinins. They tested left ventricular (LV) function using an isolated perfused heart preparation. Hearts from untreated SHRSP had indications of ischemia, as judged by low coronary flow as well as abnormalities of cardiac metabolism when compared with hearts from normotensive Wistar-Kyoto (WKY) rats. They reported that low doses of the ACE inhibitor resulted in increased LV contractility and coronary flow and improvements in metabolic indicators of ischemia. Neither blood pressure nor cardiac hypertrophy was altered; thus, the changes were independent of lowering of afterload or attenuation of cardiac hypertrophy. The antihypertensive dose of the ACE inhibitor resulted in decreased ventricular hypertrophy and normalization of the heart. Chronic treatment with a B2 kinin receptor antagonist abolished the effects of both ACE inhibitor doses on cardiac function, but the antihypertensive and antihypertrophic effects of the high ACE inhibitor dose were not affected. Thus, endogenous kinins at least partially mediate the chronic effects of ACE inhibitors on cardiac function and metabolism but play no role in their antihypertensive and antihypertrophic effects.