Is nitric oxide involved in the tonic inhibition of central sympathetic outflow in humans?
Recent studies in experimental animals have advanced the concept that neuronal nitric oxide is an important component of the signal transduction pathways that tonically restrain sympathetic vasoconstrictor outflow from the brain stem. To determine whether or not this concept can be extended to the control of sympathetic outflow in humans, we recorded muscle sympathetic nerve activity (microelectrodes, peroneal nerve) in healthy human subjects during intravenous infusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) (3.6 to 6.7 mg/kg). The major new finding is that during intravenous L-NMMA mean arterial pressure increased (10 +/- 2 mm Hg, P < .05), whereas heart rate and sympathetic nerve activity decreased (P < .05) by 10 +/- 2 beats per minute and 61 +/- 5%, respectively. These reflex decreases were indistinguishable from those produced when blood pressure was increased comparably with phenylephrine, an internal vasoconstrictor control. When the L-NMMA-induced increase in blood pressure was attenuated experimentally to minimize baroreflex activation, sympathetic nerve activity and heart rate were unchanged. Furthermore, during infusion of L-arginine (323 to 513 mg/kg IV) to increase nitric oxide synthesis, mean arterial pressure decreased (12 +/- 2 mm Hg, P < .05), but heart rate and sympathetic nerve activity increased (P < .05) by 11 +/- 2 beats per minute and 98 +/- 27%, respectively. Thus, our experiments in humans provide no support for the emerging concept that nitric oxide is involved in the tonic restraint of central sympathetic outflow.
Hansen
J
J
Department of Internal Medicine, UT Southwestern Medical Center, Dallas 75235-8573.
Jacobsen
T N
TN
Victor
R G
RG
D000328:Adult; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008839:Microelectrodes; D009132:Muscles / Q000187:drug effects; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D010543:Peroneal Nerve / Q000502:physiology; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000187:drug effects*; D019323:omega-N-Methylarginine
D010656:Phenylephrine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine