Positive inotropic effect of exogenous and endogenous NO in hypertrophic rat hearts

Abstract

1. Recent evidence suggests that nitric oxide (NO) modulates the contractile force of isolated cardiomyocytes in a biphasic manner. We sought to examine whether myocardial hypertrophy induced by long-term hypertension changes the effects of NO on myocardial contractility.

2. We used constant flow perfused non-paced Langendorff preparations of hearts of 3 months old Wistar rats (WIS, n=23) and of stroke-prone spontaneously 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 heart rate (HR) were recorded after infusion of noradrenaline (NA, 0.1 μmol  l⁻¹), glyceryl trinitrate (GTN, 1–100 μmol 1⁻¹), S-nitroso-N-acetyl-D,L-penicillamine (SNAP, 1–10 μmol 1⁻¹) and N^ω-nitro-L-arginine (L-NOARG, 0.1–1 mmol 1⁻¹).

3. Long-term hypertension induced myocardial hypertrophy and an abnormal response to NA. The relative 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 absent in SHR15. Hearts of SHR10 showed an intermediate response.

4. Both 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 increased HR. In SHR10 the lowest concentration of SNAP (1 μmol 1⁻¹) showed no effect on contractility but a significantly diminished reduction of CPP suggesting inactivation of extracellularly released NO in the coronary circulation of SHR.

5. L-NOARG significantly reduced contractility in hearts of WIS and of SHR to a similar extent. At a concentration of 1 mmol 1⁻¹ L-NOARG also reduced HR.

6. These results suggests that positive inotropic effects of exogenous and endogenous NO are not changed in hypertension induced myocardial hypertrophy.

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