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

• Published in: General pharmacology Vol. 32; no. 5; pp. 583 - 589
• Main Authors: Segarra, Gloria, Medina, Pascual, Revert, Francisco, Masiá, Salvador, Vila, José M, Such, Luis, Aldasoro, Martı́n
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.05.1999
• Subjects: Adrenergic nerves; Animals; Antihypertensive Agents - pharmacology; Cyclooxygenase Inhibitors - pharmacology; Dog pulmonary artery; Dogs; Drug Interactions; Electric Stimulation; Endothelium; Enzyme Inhibitors - pharmacology; Epoprostenol - pharmacology; Female; In Vitro Techniques; Indomethacin - pharmacology; Male; NG-Nitroarginine Methyl Ester - pharmacology; Nitric oxide; Nitric Oxide - metabolism; Norepinephrine - pharmacology; Prostaglandins - metabolism; Pulmonary Artery - drug effects; Pulmonary Artery - physiology; Vasoconstriction - drug effects; Vasodilator prostaglandins; Vasodilator prostaglandins; Dog pulmonary artery; Adrenergic nerves; Nitric oxide; Endothelium
• ISSN: 0306-3623; 1879-0011
• DOI: 10.1016/S0306-3623(98)00285-7

The aim of this work was to investigate the influence of endothelium-derived nitric oxide and prostaglandins on the contractile responses of isolated dog pulmonary arteries to electrical field stimulation and noradrenaline. Electrical field stimulation (1–8 Hz, 20 v, 0.25 ms duration, for 30 s) produced frequency-dependent contractions that were abolished by tetrodotoxin, guanethidine and, prazosin (all at 10 −6 M). Noradrenaline induced concentration-dependent contractions with an EC 50 of 1.85 × 10 −6 M. The increases in tension induced by electrical stimulation and noradrenaline were of greater magnitude in arteries denuded of endothelium. In segments with endothelium, 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 neurogenic and noradrenaline-induced contractions. The potentiation by N G-nitro- l-arginine methyl ester of electrical stimulation-induced contractile responses was partially reversed by l-arginine (10 −4 M). In the presence of N G-nitro- l-arginine methyl ester together with indomethacin the electrical stimulation-induced contractile responses were higher than those obtained when only N G-nitro- l-arginine methyl ester or indomethacin was used. N G-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 contractile response to electrical field stimulation of intramural nerves and that endothelium-derived dilator prostaglandins and nitric oxide may interact to inhibit contractile effects of adrenergic stimulation.