Positive effects of nitric oxide on left ventricular function in humans.
OBJECTIVE
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.


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 N(G)-monomethyl-l-arginine. Replenishment of the NO pool was achieved with the NO donor S-nitrosoglutathione (GSNO) (0.5 micromol 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).


CONCLUSIONS
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.
Rassaf
Tienush
T
Department of Medicine, Division of Cardiology, Pulmonary Diseases and Angiology, University Hospital Aachen, Medical Clinic I, Pauwelsstr. 30, 52074 Aachen, Germany.
Poll
Ludger W
LW
Brouzos
Paris
P
Lauer
Thomas
T
Totzeck
Matthias
M
Kleinbongard
Petra
P
Gharini
Putrika
P
Andersen
Kjel
K
Schulz
Rainer
R
Heusch
Gerd
G
Mödder
Ulrich
U
Kelm
Malte
M
D000328:Adult; D006801:Humans; D018810:Magnetic Resonance Angiography; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D013318:Stroke Volume / Q000502:physiology*; D016277:Ventricular Function, Left / Q000502:physiology*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019323:omega-N-Methylarginine; D009569:Nitric Oxide