MODULATION OF LEFT-VENTRICULAR RELAXATION IN ISOLATED EJECTING HEART BY ENDOGENOUS NITRIC-OXIDE

Nitric oxide (NO) modulates myocardial contractile behavior in several isolated preparations, e.g., cardiac myocytes and papillary muscles, via elevation of intracellular guanosine 3',5'-cyclic monophosphate (cGMP). We have recently reported that the exogenous NO donor, sodium nitroprusside, selectively modulates left ventricular (LV) relaxation in the isolated ejecting guinea pig heart, independent of coronary flow. We now report the effects of endogenously released NO on LV performance in this preparation (constant heart rate and loading). Both bradykinin (1 nM, n = 6) and substance P (100 nM, n = 6) accelerated early LV relaxation (maximum change in time constant, t(E), -10.5 +/- 1.6 and -13.4 +/- 2.1%, respectively; both P < 0.05), without significantly altering early systolic parameters (e.g., rate of LV pressure development). These effects were inhibited by hemoglobin (P < 0.05; n greater than or equal to 6), which inactivates NO. Bradykinin (100 nM, n = 10) had an additional negative inotropic effect, which was not inhibited by hemoglobin. Neither agonist altered relaxation in isolated papillary muscles. These data suggest that endogenous NO, probably released from coronary microvascular endothelial cells, modulates LV relaxation in the intact heart.