Modulation of adrenergic contraction of dog pulmonary arteries by nitric oxide and prostacyclin

The aim of this work was to investigate the influence of endothelium-derive d nitric oxide and prostaglandins on the contractile responses of isolated dog pulmonary arteries to electrical field stimulation and noradrenaline. E lectrical field stimulation (1-8 Hz, 20 v, 0.25 ms duration, for 30 s) prod uced frequency-dependent contractions that were abolished by tetrodotoxin, guanethidine and, prazosin (all at 10(-6) M). Noradrenaline induced concent ration-dependent contractions with an EC50 of 1.85 x 10(-6) M. The increase s in tension induced by electrical stimulation and noradrenaline were of gr eater magnitude in arteries denuded of endothelium. In segments with endoth elium, N-G-nitro-L-arginine methyl ester (10(-4) M) or indomethacin (10(-5) M) had no effects on the basal tone, but significantly enhanced the neurog enic and noradrenaline-induced contractions. The potentiation by N-G-nitro- L-arginine methyl ester of electrical stimulation-induced contractile respo nses was partially reversed by L-arginine (10-4 M). In the presence of NG-n itro-L-arginine methyl ester together with indomethacin the electrical stim ulation-induced contractile responses were higher than those obtained when only NG-nitro-L-arginine methyl ester or indomethacin was used. NG-nitro-L- arginine methyl ester and indomethacin did not influence neurogenic-induced contractile responses of endothelium-denuded arteries. The results suggest that endothelial cells of isolated dog pulmonary arteries depress the cont ractile response to electrical field stimulation of intramural nerves and t hat endothelium-derived dilator prostaglandins and nitric oxide may interac t to inhibit contractile effects of adrenergic stimulation. (C) 1999 Elsevi er Science Inc. All rights reserved.