Relaxation induced by histamine is not endothelium dependent in tail arteries of L-NAME-treated rats.
The present study was carried out to evaluate the relaxation induced by histamine in tail arteries of rats after chronic inhibition of nitric oxide (NO) synthesis with the inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) compared to tail arteries of control rats. The maximum relaxation induced by histamine was greater in control (88.09% +/-5.50, n=6) than in L-NAME arteries (47.33% +/-6.40, n=6), although pD(2) values were not different between the two groups (control: 4.89+/-0.08; L-NAME: 4.81+/-0.10). After incubation with 100 microM L-NAME in vitro, the maximum relaxation induced by histamine was only reduced in the control arteries (44.93% +/-2.35, n=6), whereas it had no effect on aortas of rats pretreated with this inhibitor. The incubation with 100 microM L-NAME had the same effect as endothelium removal in both arterial groups. Furthermore, the relaxation induced by histamine was unaffected by indomethacin. The combination of L-NAME and the histamine antagonist cimetidine completely abolished the relaxation induced by histamine in both arterial groups. These results show that when NO synthesis is impaired, the relaxation induced by histamine is endothelium independent, and when NO-synthase is active, the relaxation involves both NO released from endothelial cells and an endothelium-independent mechanism that is sensitive to cimetidine.
Grifoni
S C
SC
Laboratory of Pharmacology, Faculty of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. do Café s/no., SP-14040-903, Ribeirão Preto, Brazil.
Bendhack
L M
LM
D000818:Animals; D001158:Arteries / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D013623:Tail / Q000098:blood supply*
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D006632:Histamine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin