Cardiac angiotensin converting enzyme and diastolic function of the heart.

It has been known for a long time that systemic infusion of angiotensin II in patients with coronary artery disease or normal control subjects causes a marked increase in left ventricular end diastolic pressure (LVEDP) and systolic pressure (LVP) (1,2). In this setting angiotensin II produces a marked increase in afterload that makes it difficult to acknowledge possible local myocardial effects of the peptide. The studies (3-8) summarized in the present paper were designed to examine the physiological role of local cardiac angiotensin II generation and local bradykinin degradation on cardiac function in the normal and hypertrophied rat heart. Angiotensin I and angiotensin II, infused in isolated, well oxygenated, buffer perfused normal rat hearts, produced a mild increase in LVEDP with no change in systolic function (3). In contrast, in hypertrophied rat hearts, angiotensin I and angiotensin II caused a marked deterioration of diastolic function, increasing LVEDP from 10 to 25-37 mmHg on average (3,5). Preliminary evidence suggests that angiotensin II effects on diastolic function are mediated via a protein kinase C dependent pathway that might involve Na+/H+ exchange (4,5). When cardiac angiotensin converting enzyme was blocked by infusion of an ACE inhibitor prior and in parallel to angiotensin I infusion no changes in diastolic function were noted (6). Furthermore, ACE inhibition blunted the diastolic dysfunction during low flow ischemia in isolated hypertrophied rat hearts (7). This effect of ACE inhibition was even more remarkeable, since no exogenous angiotensin was infused in this experiment.(ABSTRACT TRUNCATED AT 250 WORDS)