Influence of endothelial nitric oxide on neurogenic contraction of human pulmonary arteries

Abstract

I In nf fl lu ue en nc ce e o of f e en nd do ot th he el li ia al l n ni it tr ri ic c o ox xi id de e o on n n ne eu ur ro og ge en ni ic c c co on nt tr ra ac ct ti io on n o of f h hu um ma an n p pu ul lm mo on na ar ry y a ar rt te er ri ie es s ABSTRACT: The present study was designed to investigate the contribution of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human pulmonary arteries to electrical field stimulation (EFS) and noradrenaline. Isometric tension was measured in artery rings obtained from portions of human lung after thoracic surgery for removal of lung carcinoma (18 patients).Electrical field stimulation (EFS) induced frequency-dependent contractions of isolated human pulmonary arteries which were abolished by tetrodotoxin, guanethidine and prazosin (all at 10 -6 M). The increases in tension were of greater magnitude in arteries denuded of endothelium. N G -nitro-L-arginine methyl ester (L-NAME) (10 -4 M) potentiated the contractile response to EFS in artery rings with endothelium but not in endothelium-denuded arteries. The potentiation induced by L-NAME was completely reversed by L-arginine (10 -4 M) but not by D-arginine (10 -4 M). Indomethacin (3×10 -6 M) had no significant effect on the contractile response to EFS. Contractile responses to noradrenaline were similar in arteries with and without endothelium.Our results suggest that electrical field stimulation releases endothelium-derived nitric oxide, which inhibits the contractile responses of human pulmonary arteries. Although adrenergic nerves seem to be responsible for the contraction, the transmitter involved in the release of nitric oxide does not appear to be noradrenaline.

Neurogenic contraction and relaxation of human penile deep dorsal vein

“…The neurogenic contraction observed in the present study is more than 30% (at 2 Hz) of the maximal contraction to KCl. This response is higher than the maximal neural‐mediated contraction in human pulmonary (20 ± 3.6% of KCl), mesenteric (7.7 ± 2.0% of KCl) and deferential (10.6 ± 2.7% of KCl) arteries removed at surgery using the same experimental setup (Aldasoro et al , 1993; Martinez et al , 1994; 1995). The resulting neurogenic contraction is apparently mediated, to a great extent, by the release of the adrenergic transmitter which in turn activates the α 1 ‐adrenoceptors.…”

“…In approximately 50% of the venous rings the endothelium was removed mechanically by inserting a roughened stainless steel wire into the lumen and gently rubbing the ring on a wet filter paper. This procedure has been shown morphologically to result in essentially complete removal of the endothelium (Martínez et al , 1994; 1995). Functional integrity of the endothelium was confirmed routinely by the presence of relaxation induced by acetylcholine (10 −7 ‐10 −6 m) or substance P (10 −9 ‐10 −8 M) during contraction obtained with noradrenaline (10 −7 ‐3 × 10 −7 M).…”

“…Electrical field stimulation was provided by a Grass S88 stimulator (Grass Instruments, Quincy, U.S.A.) via two platinum electrodes positioned on each side and parallel to the axis of the venous ring. To assess the nature of the contractile responses and avoid direct stimulation of smooth muscle, frequency‐response relationships were determined on a group of veins in the presence and absence of 10 −6 m tetrodotoxin, following procedures previously described (Aldasoro et al , 1993; Martinez et al , 1994; 1995). In summary, the protocol was designed to find the optimal stimulation parameters causing a contractile response that was completely eliminated by 10 −6 M tetrodotoxin.…”

Mediators of Asthma: Nitric oxide

“…38 NO is a the i-NANC response, in human airways the major potent vasodilator in the bronchial circulation and neurotransmitter of the i-NANC pathway is NO, may play an important modulatory role in the pulbecause different NOS inhibitors virtually abolish the monary circulation. [39][40][41][42] i-NANC response. 31,33 Also, i-NANC stimulation of By acting as i-NANC neurotransmitter it mediates human airways results in an increase in cyclic GMP cholinergic reflexes, 43 adrenergic contraction [44][45][46] and but not cyclic AMP levels (Ward et al, 1995a).…”

Increased responsiveness of human pulmonary arteries in patients with positive bronchodilator response

“…The mechanisms involved in these responses are unknown at present but probably reflect an increase in sensitivity of smooth muscle to these agonists, as was observed for nitric oxide. There appears to be no endothelial receptors for endothelin and noradrenaline in human pulmonary arteries (McKay et al, 1991;Martinez et al, 1995). The increased responsiveness to noradrenaline observed in chronic lung disease appears to be due to the impairment of nitric oxide-mediated relaxation which occurs in these patients (Dinh-Xuan 1991).…”