The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels

• Published in: Pharmacological reviews Vol. 55; no. 2; pp. 271 - 324
• Main Authors: Toda, Noboru, Okamura, Tomio
• Format: Journal Article
• Language: English
• Published: United States American Society for Pharmacology and Experimental Therapeutics 01-06-2003
• Subjects: Animals; Humans; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Muscle, Smooth, Vascular - physiology; Nitric Oxide - pharmacology; Nitric Oxide - physiology; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase - physiology; Peripheral Nervous System - drug effects; Peripheral Nervous System - metabolism; Peripheral Nervous System - physiology
• ISSN: 0031-6997; 1521-0081
• DOI: 10.1124/pr.55.2.3

Unanticipated, novel hypothesis on nitric oxide (NO) radical, an inorganic, labile, gaseous molecule, as a neurotransmitter
first appeared in late 1989 and into the early 1990s, and solid evidences supporting this idea have been accumulated during
the last decade of the 20th century. The discovery of nitrergic innervation of vascular smooth muscle has led to a new understanding
of the neurogenic control of vascular function. Physiological roles of the nitrergic nerve in vascular smooth muscle include
the dominant vasodilator control of cerebral and ocular arteries, the reciprocal regulation with the adrenergic vasoconstrictor
nerve in other arteries and veins, and in the initiation and maintenance of penile erection in association with smooth muscle
relaxation of the corpus cavernosum. The discovery of autonomic efferent nerves in which NO plays key roles as a neurotransmitter
in blood vessels, the physiological roles of this nerve in the control of smooth muscle tone of the artery, vein, and corpus
cavernosum, and pharmacological and pathological implications of neurogenic NO have been reviewed. This nerve is a postganglionic
parasympathetic nerve. Mechanical responses to stimulation of the nerve, mainly mediated by NO, clearly differ from those
to cholinergic nerve stimulation. The naming “nitrergic or nitroxidergic” is therefore proposed to avoid confusion of the
term “cholinergic nerve”, from which acetylcholine is released as a major neurotransmitter. By establishing functional roles
of nitrergic, cholinergic, adrenergic, and other autonomic efferent nerves in the regulation of vascular tone and the interactions
of these nerves in vivo, especially in humans, progress in the understanding of cardiovascular dysfunctions and the development
of pharmacotherapeutic strategies would be expected in the future.