The pharmacology of nitric oxide in the peripheral nervous system of blood vessels

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.