Functional Study on Nitroxidergic Nerve in Isolated Dog Pulmonary Arteries and Veins

Abstract

ABSTRACT-In dog pulmonary arterial and venous strips without endothelium under treatment with prazosin, nicotine induced relaxation that was abolished by N G -nitro-L-arginine, hexamethonium and methylene blue. L-Arginine antagonized the N G -nitro-L-arginine action. Neurogenic relaxations tended to be more evident in the vein. Nitric oxide (NO)-induced relaxations were greater in the veins than in the arteries. Concentrations of NO to induce the same magnitude of relaxation as that to nicotine were higher in the arteries. In conclusion, dog pulmonary arteries and veins are innervated by nitroxidergic (nitrergic) nerves, and NO is released by nerve stimulation with nicotine in a larger amount in the artery than the vein.Keywords: Nicotine, Nitroxidergic (nitrergic) nerve, Pulmonary vasculature Inhalation of nitric oxide (NO) is recognized as a useful therapy for primary pulmonary hypertension, persistent pulmonary hypertension of the neonate and adult respiratory distress syndrome (1). The effect is considered to be due mainly to reduced arterial resistance and also to bronchiolar smooth muscle relaxation. Endogenous NO derived from the endothelium (2) or autonomic efferent nerve (3, 4) of pulmonary arteries is expected to play an important role in the regulation of vascular resistance.Inhaled NO acts mainly on pulmonary arterioles via alveoli, thus resulting in therapeutic effectiveness locally. Intravenously applied NO donors, such as nitroglycerin, nitroprusside, Sin 1, etc., and endothelium-derived NOreleasing substances also act on pulmonary veins and systemic vasculature. Some studies have indicated the different responsiveness to chemical stimuli of pulmonary arteries and veins (2, 5, 6). However, no information is available concerning quantitative analyses of the heterogeneous response to nitroxidergic nerve stimulation and NO in the arteries and veins.There is a discrepancy in mechanisms of neurogenic vasodilatation in pulmonary arteries. It has been reported that NO is involved in vasodilation of the guinea pig pulmonary arteries (3, 4), whereas CGRP acts as a neurotransmitter in the same arteries (7,8).The aim of the present study was to clarify the mechanism underlying neurogenic relaxation and to determine different responsiveness to chemical perivascular nerve stimulation by nicotine and exogenously applied NO of canine pulmonary arteries and veins. The nicotine-induced response is considered to be caused by nerve stimulation from the functional and histological studies in canine penile veins (9). Beagle dogs of either sex, weighing 9 to 13 kg, were used for the present study. The Animal Care and Use Committee at our University approved the use of dog blood vessels. The dogs were anesthetized with thiopental sodium (20 mg /kg, i.v.) and killed by bleeding from carotid arteries. Lungs were rapidly removed. Second or third branches of intrapulmonary arteries and accompanying veins (0.7 -0.9 mm diameter) were isolated and helically cut into strips of approx. 20-mm length. The endothelium was removed b...

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

“…Endotheliumindependent, TTX-sensitive neurogenic relaxations are mainly mediated by NO in guinea pig pulmonary arteries (Liu et al, 1992a;Scott and McCormack, 1999) and the endothelium-dependent, TTX-sensitive response is mediated by NO and additional neurotransmitters in rat pulmonary arteries (Gumusel et al, 2001). Nicotine caused relaxation in canine pulmonary arteries and veins that was abolished by C 6 and L-NA (Ayajiki et al, 2002). The venous relaxation was greater than the arterial one.…”

Control of systemic and pulmonary blood pressure by nitric oxide formed through neuronal nitric oxide synthase

“…Furthermore, there is some reported evidence indicating that peripheral arteries, such as mesenteric [23][24][25], renal [26], pulmonary [27], ocular [28,29], lingual [30], and cutaneous arteries [31], in a variety of mammals including monkeys are innervated by nitrergic nerves that contribute to counteracting vasoconstrictor sympathetic nerve functions. Transmural electrical stimulation or nicotine has been used to stimulate perivascular nerves to liberate neurotransmitters, such as norepinephrine and nitric oxide, in vitro and in vivo.…”

“…Pulmonary vasodilatation induced by perivascular nerve stimulation is mediated mainly by nitric oxide formed by nNOS [27,77,78]. NOS inhibitors increased the pulmonary arterial pressure response to hypoxia in isolated rat lungs [79,80].…”

Neurally-derived nitric oxide regulates vascular tone in pulmonary and cutaneous arteries of the toad,Bufo marinus

“…39). In addition to the endothelium, nitrergic nerves are also thought to provide nonadrenergic, noncholinergic vasodilation of the pulmonary vasculature (3,27,28,42).The mechanism of vascular NO signaling in amphibians is controversial because there are conflicting data on whether NO is derived from the endothelium or perivascular nerves. Initial studies on the presence of an endothelially derived relaxing factor showed that ACh mediated an endothelium-dependent vasodilation in the systemic vasculature (25, 31), which was abolished by the NO synthase (NOS) inhibitor N -nitro-Larginine methyl ester in leopard frog (25).…”

“…39). In addition to the endothelium, nitrergic nerves are also thought to provide nonadrenergic, noncholinergic vasodilation of the pulmonary vasculature (3,27,28,42).…”