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-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 EC50, of 1.85 x 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.
Segarra
G
G
Department of Physiology, University of Valencia, Spain.
Medina
P
P
Revert
F
F
Masiá
S
S
Vila
J M
JM
Such
L
L
Aldasoro
M
M
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004285:Dogs; D004347:Drug Interactions; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000378:metabolism; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*
D000959:Antihypertensive Agents; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D009569:Nitric Oxide; D011464:Epoprostenol; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine; D007213:Indomethacin