ANGIOTENSIN-CONVERTING ENZYME-INHIBITION IMPROVES CARDIAC-FUNCTION - ROLE OF BRADYKININ

The effect of chronic low- and high-dose treatment with the angiotensi n-converting enzyme (ACE) inhibitor ramipril (0.01 and 1 mg/kg per day ) on the development of hypertension and left ventricular hypertrophy as well as on functional and biochemical alterations of the heart was studied in stroke-prone spontaneously hypertensive rats treated prenat ally and subsequently up to the age of 20 weeks. The contribution of e ndogenous bradykinin potentiation to the ACE inhibitor actions was ass essed by cotreatment of rats with the bradykinin B2-receptor antagonis t Hoe 140 (500 mu g/kg per day SC) from 6 to 20 weeks of age. High- bu t not low-dose ACE inhibitor treatment prevented the development of hy pertension and left ventricular hypertrophy. Chronic bradykinin recept or blockade did not attenuate the antihypertensive and antihypertrophi c actions of ramipril. High-dose ramipril treatment improved cardiac f unction, as demonstrated by an increase in left ventricular pressure ( 29.9%), dP/dt(max) (34.9%), and coronary flow (22.1%), without a chang e in heart rate. The activities of lactate dehydrogenase and creatine kinase and lactate concentration in the coronary effluent were reduced by 39.3%, 55.5%, and 66.7%, respectively. Myocardial tissue concentra tions of glycogen and the energy-rich phosphates ATP and creatine phos phate were increased by 31.3%, 39.9%, and 73.7%, respectively, whereas lactate was decreased by 20.8%. Chronic low-dose ACE inhibitor treatm ent led to a pattern of changes in cardiodynamics and cardiac metaboli sm similar to that observed with the high dose. All ACE inhibitor-indu ced effects on cardiac function and metabolism were abolished by chron ic bradykinin receptor blockade. Our results demonstrate that chronic ACE inhibitor treatment in stroke-prone spontaneously hypertensive rat s improves cardiac function even at low doses that do not affect the d evelopment of hypertension and left ventricular hypertrophy. These eff ects of the ACE inhibitor are due to bradykinin potentiation. However, bradykinin does not seem to contribute to the antihypertensive and an tihypertrophic actions of the ACE inhibitor in this model of hypertens ion.