EFFECTS OF INHIBITING NEUTRAL ENDOPEPTIDASE AND KININASE-II ON CORONARY AND SYSTEMIC HEMODYNAMICS IN RATS

To determine whether neutral endopeptidase (NEP) and kininase II (angi otensin-converting enzyme, ACE) influence coronary hemodynamics, we co mpared the effects of inhibiting NEP, ACE, or both before and after is oproterenol (50 mg/kg ip). We measured flow and resistance using radio active microspheres in 90 anesthetized rats which received the NEP inh ibitor phosphoramidon (2.5 mg/kg), the ACE inhibitor captopril (2.5 mg /kg), both combined, or vehicle alone. Before isoproterenol, inhibitin g NEP, ACE, or both increased left ventricular blood flow by 48 +/- 10 (SE), 33 +/- 9, and 10 +/- 6%, respectively and decreased left ventri cular vascular resistance by 26 +/- 6, 31 +/- 10, and 10 +/- 6%, respe ctively. After isoproterenol, NEP inhibition augmented the decrease in left ventricular vascular resistance (25 +/- 6% decrease within 90 s of isoproterenol vs. 8 +/- 5% in controls). ACE inhibition did not aug ment the decrease in resistance but inhibiting both enzymes did so to a lesser extent than inhibiting NEP. These effects cannot be explained by vascular responses secondary to changes of myocardial oxygen consu mption. We conclude that NEP and ACE are regulators of myocardial bloo d flow.