An inhibitor of nitric oxide synthase does not increase contraction or beta-adrenoceptor sensitivity of ventricular myocytes from failing human heart

Objective: Nitric oxide (NO) has been implicated in the depression of cardiac function in human heart failure. Some reports have identified iNOS (inducible nitric oxide synthase) within the myocyte component of the failing human heart, and NO is known to decrease the contraction amplitude of isolated ventricular myocytes. We have treated myocytes from failing human ventricle with a NOS inhibitor, N G-monomethyl-l-arginine (L-NMMA), in an attempt to restore contractile function. Methods and Results : Myocytes were isolated from failing and non-failing human ventricles and their contraction amplitude was measured during superfusion (32°C, 1–2 mmol/l Ca2+) and electrical stimulation (0.1–2 Hz). The contraction amplitude of myocytes from failing hearts was depressed in a frequency-dependent manner. At 1 Hz, the contraction amplitude of cells from non-failing heart was 4.70±0.53% cell shortening (mean±SEM, n =13 subjects), compared with 2.18±0.27% ( P