Interaction between nitric oxide and the cholinergic and sympathetic nervous system in cardiovascular control in humans.
Evidence has accumulated indicating that the interaction between NO and the autonomic nervous system plays an important role in cardiovascular regulation, not only in experimental animals, but also in humans. NO interacts with the autonomic nervous system both at the central level and peripherally. In this review, we will summarize the current understanding of this interaction in normal humans, and discuss pathophysiological consequences that occur, when this interaction is altered. We provide evidence for the concept that the primary effect of NO in humans is a reduction of basal sympathetic vasoconstrictor tone, rather than inhibition of the excitability of this system. Impaired NO synthesis in humans therefore promotes sustained vasoconstriction by 2 distinct mechanisms: loss of vasodilator tone at vascular smooth muscle cells and by facilitating central neural vasoconstrictor outflow. Insulin resistance, essential hypertension and end-stage renal failure are examples of diseases, where impaired NO buffering of neural outflow may contribute to sustained sympathetic activation. In addition to the sympathetic nervous system, NO also interacts with the cholinergic nervous system. Cholinergic mechanisms play a major, hitherto unrecognised, role in offsetting the arterial hypertension and cardiac sympathetic activation caused by inhibition of NO synthesis in normal humans. While further studies are needed to determine the exact underlying mechanism(s) by which NO and the autonomic nervous system interact in humans, these findings provide the conceptual framework for the use of therapeutic interventions that deliver NO and/or modulate the bioavailability of endogenously produced NO to adjust the autonomic control of the circulation in humans.
Sartori
Claudio
C
Botnar Center for Clinical Research, Department of Internal Medicine, BH 10.642, Centre Hospitalier Universitaire Vaudois, CH-1011 Lausanne, Switzerland.
Lepori
Mattia
M
Scherrer
Urs
U
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004347:Drug Interactions; D045462:Endothelium-Dependent Relaxing Factors / Q000494:pharmacology / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D009569:Nitric Oxide / Q000096:biosynthesis / Q000494:pharmacology / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D045462:Endothelium-Dependent Relaxing Factors; D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D009569:Nitric Oxide