Histamine-induced relaxation in pulmonary artery of normotensive and hypertensive rats: relative contribution of prostanoids, nitric oxide and hyperpolarization.
The aim of this study was to determine the relative contribution of nitric oxide (NO), endothelium-derived hyperpolarizing factor (EDHF) and prostanoids in histamine-induced relaxation of isolated pulmonary artery from normotensive and hypertensive rats. The hypertension was induced by oral administration of NO synthase inhibitor N(G)-nitro-L-arginine methylester (L-NAME, 50 mg/kg/day) to normotensive rats for 8 weeks. In phenylephrine-precontracted arterial rings the histamine-induced relaxation was significantly reduced in L-NAME-treated rats compared to the controls. Indomethacin (cyclooxygenase inhibitor) and glibenclamide (ATP-sensitive K+-channel blocker) did not inhibit the relaxation response in either control or hypertensive rats. On the other hand, tetraethylammonium (TEA), a K+-channel blocker with a broad specificity, significantly reduced histamine-induced relaxation in the pulmonary artery from both groups examined. The TEA-resistant relaxation was completely abolished by additional administration of L-NAME to the incubation medium. The results indicate that histamine-induced relaxation of the pulmonary artery in both normotensive and hypertensive rats is mediated mainly by nitric oxide, whereas EDHF seems to play a minor role.
Török
J
J
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovakia. torok@unpf.savba.sk
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000502:physiology; D011453:Prostaglandins / Q000502:physiology*; D011651:Pulmonary Artery / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011453:Prostaglandins; D009569:Nitric Oxide; D006632:Histamine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin