Histamine-Induced Relaxation in Pulmonary Artery of Normotensive and Hypertensive Rats: Relative Contribution of Prostanoids, Nitric Oxide and Hyperpolarization

J. TÖRÖK

Received August 15, 1999
Accepted September 21, 1999

Summary
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.

Key words
Pulmonary artery · Histamine · Nitric oxide · EDHF

Reprint requests
Dr. J. Török, Institute of Normal and Pathological Physiology Slovak Academy of Sciences, Sienkiewiczova 1, 813 71 Bratislava, Slovak Republic. E-mail: torok@unpf.savba.sk