© 1998 by European Society of Cardiology
Copyright © 1998, European Society of Cardiology
An inhibitor of nitric oxide synthase does not increase contraction or β-adrenoceptor sensitivity of ventricular myocytes from failing human heart
Imperial College School of Medicine at the National Heart and Lung Institute, Dovehouse Street, London SW3 6LY, UK
* Corresponding author. Tel.: +44-171-352-8121 ext. 3311; fax: +44-171-823-3392; e-mail: sian.harding@ic.ac.uk
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, NG-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<0.01, 11 patients) from patients with ischaemic heart disease (IHD) or 2.56±0.74% (P<0.02, six patients) with dilated cardiomyopathy (DCM). Superfusion with 0.1 mmol/l L-NMMA did not increase contraction amplitude in myocytes from failing heart at either 0.2 Hz (n=11) or 1 Hz (n=7). Responses to β-adrenoceptor stimulation were reduced in myocytes from failing human heart, with contraction amplitude in maximum isoprenaline 0.47±0.11 of that in high Ca2+ in the same cell (n=6), compared to 0.99±0.07 in non-failing heart (n=14, P<0.01). The presence of 0.1 mmol/l L-NMMA did not increase the isoprenaline/Ca2+ ratio in myocytes from failing heart (0.40±0.09, P=NS). Conclusion: These results do not suggest a functional role for tonic NO production in the frequency-dependent depression of contraction or β-adrenoceptor desensitisation in myocytes from failing human ventricle.
KEYWORDS Nitric oxide; Heart failure; Frequency; Contractility; Human
1 Present address: Department of Cardiovascular Medicine, John Radcliffe Hospital, Oxford OX3 9DU, UK.
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