(Circulation. 1997;96:3897-3903.)
© 1997 American Heart Association, Inc.
Articles |
Cardiovascular and Sympathetic Effects of Nitric Oxide Inhibition at Rest and During Static Exercise in Humans
From the Department of Internal Medicine B, Centre Hospitalier Universitaire Vaudois, Lausanne (R.O., C.S., M.L., P.N., U.S.), and the Institute of Physiology, University of Lausanne (L.V., L.T.), Switzerland.
Correspondence to Dr Urs Scherrer, Department of Internal Medicine, BH 10.642, CHUV, CH-1011 Lausanne, Switzerland. E-mail Urs.Scherrer{at}chuv.hospvd.ch
Background Nitric oxide (NO) regulates vascular tone and blood pressure, and studies in animals suggest that it does so, at least in part, by modulating sympathetic neural outflow. Loss of NO-induced vasodilator tone and restraint on sympathetic vasoconstrictor outflow could lead to exaggerated vasoconstrictor and pressor responses to physical stress in humans.
Methods and Results To determine the role of NO in the modulation
of central sympathetic outflow and vascular tone at rest and during a
physical stress, we tested effects of systemic inhibition of NO
synthase by
NG-monomethyl-L-arginine
(L-NMMA) infusion (a stereospecific inhibitor of NO
synthase) on sympathetic nerve activity (microneurography), regional
vascular resistance, and blood pressure at rest and during static
handgrip. The major new findings are that (1) under resting conditions,
L-NMMA infusion, which increased mean arterial pressure by
10%, did not have any detectable effect on muscle sympathetic nerve
activity, whereas a similar increase in arterial pressure
evoked by phenylephrine infusion (an NO-independent
vasoconstrictor) decreased the rate of sympathetic nerve firing by
50%; (2) during static handgrip, the exercise-induced sympathetic
nerve responses were preserved during L-NMMA infusion but markedly
attenuated during phenylephrine infusion; and (3) the
L-NMMA–induced loss of vasodilator tone did not result in exaggerated
exercise-induced pressor and calf vasoconstrictor responses.
Conclusions These findings indicate that NO is involved in the central regulation of sympathetic outflow in humans and suggest that both neuronal and endothelial NO synthesis may contribute to the regulation of vasomotor tone.
Key Words: nervous system, autonomic • endothelium • exercise • endothelium-derived factors
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