European Heart Journal Advance Access originally published online on June 16, 2006
European Heart Journal 2006 27(14):1699-1705; doi:10.1093/eurheartj/ehl096
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Positive effects of nitric oxide on left ventricular function in humans
1 Department of Medicine, Division of Cardiology, Pulmonary Diseases and Angiology, University Hospital Aachen, Medical Clinic I, Pauwelsstr. 30, 52074 Aachen, Germany
2 Institute of Diagnostic Radiology, Heinrich-Heine-University, Duesseldorf, Germany
3 Institute of Pathophysiology, Medical School, University of Essen Germany
Received 14 February 2006; revised 17 May 2006; accepted 26 May 2006; online publish-ahead-of-print 16 June 2006.
* Corresponding author. Tel: +49 241 8089301; fax: +49 241 8082049. E-mail address: mkelm{at}ukaachen.de
Aims The myocardial effect of tonically released nitric oxide (NO) in humans is still not known. We tested the hypothesis that low-dose NO exerts positive effects on left ventricular (LV) function.
Methods and results Twelve healthy volunteers, 26±4 years, were enrolled in this study. Magnetic resonance imaging was used to precisely measure the direct effects of NO on stroke volume index (SVI). The NO pool was monitored by chemiluminescence. We reduced endogenous NO levels with intravenous infusion of the NO synthase-inhibitor NG-monomethyl-L-arginine. Replenishment of the NO pool was achieved with the NO donor S-nitrosoglutathione (GSNO) (0.5 µmol iv). To differentiate load-dependent from the direct effects of NO on LV function, changes in SVI in response to GSNO were compared with changes in the NO-independent vasodilator dihydralazine (2.5 mg iv) at matched arterial pressure and heart rate. Inhibition of NO synthesis was followed by reduction in SVI. Subsequent replenishment of the circulating NO with GSNO significantly increased SVI (39±8 to 54±7 mL m–2; P=0.001), whereas no significant changes were observed with the NO-independent vasodilator dihydralazine (39±8 to 46±8 mL m–2; P=0.0626).
Conclusion Inhibition of endogenous NO release reduces, whereas replenishment with exogenous NO increases LV function, pointing towards a positive effect of tonically released NO on LV function in healthy humans.
Key Words: Endothelium • Nitric oxide • MRI • LV function • Myocardium
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