Histamine H1-receptor antagonists do not prevent the appearance of endothelium-dependent relaxation to acetylcholine in rat pulmonary artery.
The purpose of this study was to determine the relaxant effects of acetylcholine after inhibition of vascular histaminergic receptors. In isolated rings of the rat pulmonary artery precontracted by phenylephrine (10(-5) mol/l) both histamine (10(-7) to 10(-4) mol/l) and acetylcholine (10(-8) to 3 x 10(-5) mol/l) produced concentration-dependent relaxations. The arterial relaxations induced by either histamine or acetylcholine were markedly reduced or abolished by administration of NO synthase inhibitor NG-nitro-L-arginine methyl ester (10(-5) mol/l). Relaxant responses to histamine were not influenced by cimetidine, histamine H2-receptor antagonist, but were significantly decreased or abolished by treatment with chlorphenyramine or diphenhydramine, histamine H1-receptor antagonists. On the other hand, chlorphenyramine and diphenhydramine did not prevent the appearance of endothelium-dependent relaxation to acetylcholine. The results suggest that relaxation to histamine in the rat pulmonary artery is mediated by H1-histaminergic receptors and their inactivation does not interfere with the endothelial capability to produce and/or release nitric oxide by the activation of other types of receptors.
Kyselá
S
S
Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Török
J
J
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002744:Chlorpheniramine / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects* / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D011651:Pulmonary Artery / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011969:Receptors, Histamine H1 / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011969:Receptors, Histamine H1; D002744:Chlorpheniramine; D002927:Cimetidine; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester