POTENTIATION OF ENDOGENOUS BRADYKININ (BK ) BY PERINDOPRIL IMPROVES CARDIAC-FUNCTION AND MYOCARDIAL-METABOLISM IN SHRSP

SHRsp were treated in utero and, subsequently, up to the age of 20 wee ks with low-dose perindopril (10 mug/kg per day). The contribution of endogenous BK to the actions of the ACE inhibitor was assessed by chro nic BK receptor blockade and by measurement of myocardial prostacyclin and cGMP concentrations. Perindopril at the dose used had no effect o n the development of hypertension and left ventricular hypertrophy. Ho wever, perindopril improved cardiac function as demonstrated by an inc rease in left ventricular pressure and dp/dtmax without change in hear t rate. The activities of LDH and creatine kinase as well as lactate c oncentrations in the coronary effluent were reduced and myocardial tis sue concentrations of glycogen, ATP and creatine kinase were increased . All ACE inhibitor-induced effects were abolished by concomitant chro nic BK receptor blockade. Cardiac prostacyclin concentrations were 3-f old elevated in perindopril-treated animals while cGMP levels remained unchanged when compared to controls. Our data demonstrate that chroni c low-dose ACE inhibitor treatment can improve cardiac function and me tabolism by potentiation of endogenous BK. These effects are independe nt of the antihypertensive and antihypertrophic drug actions and may b e mediated by prostacyclin generation.