POSITIVE INOTROPIC EFFECT OF EXOGENOUS AND ENDOGENOUS NO IN HYPERTROPHIC RAT HEARTS

1 Recent evidence suggests that nitric oxide (NO) modulates the contra ctile force of isolated cardiomyocytes in a biphasic manner. We sought to examine whether myocardial hypertrophy induced by long-term hypert ension changes the effects of NO on myocardial contractility. 2 We use d constant flow perfused non-paced Langendorff preparations of hearts of 3 months old Wistar rats (WIS, n=23) and of stroke-prone spontaneou sly hypertensive rats (SHR) at the age of 10 months (SHR10, n=16) and 15 months (SHR15, n=8). Changes of left ventricular peak pressure (LVP ), +dP/dt(max), -dP/dt(max), coronary perfusion pressure (CPP) and hea rt rate (HR) were recorded after infusion of noradrenaline (NA, 0.1 mu mol l(-1)), glyceryl trinitrate (GTN, 1-100 mu mol l(-1)), S-nitroso- N-acetyl-D,L-penicillamine (SNAP, 1-10 mu mol l(-1)) and N-omega-nitro -L-arginine (L-NOARG, 0.1-1 mmol l(-1)). 3 Long-term hypertension indu ced myocardial hypertrophy and an abnormal response to NA. The relativ e heart weight (in mg kg(-1)) increased from 2.95+/-0.04 (WIS) to 6.67 +/-0.34 (SHR15), while the increase in +dP/dt(max) induced by NA was a bsent in SHR15. Hearts of SHR10 showed an intermediate response. 4 Bot h SNAP and GTN significantly increased LVP, +dP/dt(max) and -dP/dt(max ) in hearts of WIS and of SHR. In WIS but not in SHR10, SNAP also incr eased HR. In SHR10 the lowest concentration of SNAP (1 mu mol l(-1)) s howed no effect on contractility but a significantly diminished reduct ion of CPP suggesting inactivation of extracellularly released NO in t he coronary circulation of SHR. 5 L-NOARG significantly reduced contra ctility in hearts of WIS and of SHR to a similar extent. At a concentr ation of 1 mmol l(-1) L-NOARG also reduced HR. 6 These results suggest s that positive inotropic effects of exogenous and endogenous NO are n ot changed in hypertension induced myocardial hypertrophy.