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 prostanoi ds in histamine-induced relaxation of isolated pulmonary artery from normot ensive and hypertensive rats. The hypertension was induced by oral administ ration of NO synthase inhibitor NG-nitro-L-arginine methylester (L-NAME, 50 mg/kg/day) to normotensive rats for 8 weeks. In phenylephrine-precontracte d arterial rings the histamine-induced relaxation was significantly reduced in L-NAME-treated rats compared to the controls. Indomethacin (cyclooxygen ase 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 broa d specificity, significantly reduced histamine-induced relaxation in the pu lmonary artery from both groups examined. The TEA-resistant relaxation was completely abolished by additional administration of L-NAME to the incubati on medium. The results indicate that histamine-induced relaxation of the pu lmonary artery in both normotensive and hypertensive rats is mediated mainl y by nitric oxide, whereas EDHF seems to play a minor role.