Effects of inhibiting neutral endopeptidase and kininase II on coronary and systemic hemodynamics in rats.
To determine whether neutral endopeptidase (NEP) and kininase II (angiotensin-converting enzyme, ACE) influence coronary hemodynamics, we compared the effects of inhibiting NEP, ACE, or both before and after isoproterenol (50 mg/kg ip). We measured flow and resistance using radioactive microspheres in 90 anesthetized rats which received the NEP inhibitor phosphoramidon (2.5 mg/kg), the ACE inhibitor captopril (2.5 mg/kg), both combined, or vehicle alone. Before isoproterenol, inhibiting NEP, ACE, or both increased left ventricular blood flow by 48 +/- 10 (SE), 33 +/- 9, and 10 +/- 6%, respectively, and decreased left ventricular vascular resistance by 26 +/- 6, 31 +/- 10, and 10 +/- 6%, respectively. 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 augment 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 consumption. We conclude that NEP and ACE are regulators of myocardial blood flow.
Maxwell
A J
AJ
Cardiovascular Research Institute, University of California, San Francisco, California 94143, USA.
Husseini
W K
WK
Piedimonte
G
G
Hoffman
J I
JI
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D015260:Neprilysin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D007703:Peptidyl-Dipeptidase A / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D007703:Peptidyl-Dipeptidase A; D015260:Neprilysin; D007545:Isoproterenol