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Analysis of the depressant effect of the endothelium on contractions of rabbit isolated basilar artery to 5‐hydroxytryptamine
Author(s) -
Trezise D.J.,
Drew G.M.,
Weston A.H.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14380.x
Subject(s) - endothelium , endothelium derived relaxing factor , contraction (grammar) , endothelium derived hyperpolarizing factor , endocrinology , chemistry , basilar artery , vasodilation , medicine , acetylcholine , nitric oxide , nitroarginine , pharmacology , nitric oxide synthase , charybdotoxin
1 The effects of endothelium removal and of a number of pharmacological agents known to modify endothelial cell function on the contractile response of rabbit isolated basilar arteries to 5‐hydroxytryptamine (5‐HT) and other vasoconstrictors were studied. 2 Endothelium removal slightly reduced the contractile response to potassium chloride (40 m m ) but markedly augmented and potentiated contractions to 5‐HT (1 n m − 10 μ m ). 3 l ‐N G ‐nitro‐arginine ( l ‐NOARG, 1–30 μ m ), an inhibitor of nitric oxide formation in vascular endothelial cells, evoked endothelium‐dependent contraction, and augmented and potentiated contractions to 5‐HT in endothelium‐intact but not endothelium‐denuded tissues. Prior incubation with l ‐arginine (1 m m ), but not d ‐arginine (1 m m ), abolished these effects of l ‐NOARG (1 μ m ). l ‐NOARG (30 μ m ) also augmented contractions of endothelium‐intact tissues to noradrenaline, prostaglandin F 2α , and to a lesser degree endothelin‐1. 4 Neither glibenclamide (3 μ m ) nor N‐ethylmaleimide (1 μ m ), putative inhibitors of the effects of endothelium‐derived hyperpolarizing factor (EDHF) and of agonist‐stimulated endothelium‐derived relaxing factor (EDRF) release respectively, had any effect on either resting tension or the contractile response to 5‐HT. In some tissues indomethacin (3 μ m ), a cyclo‐oxygenase inhibitor, produced a small contraction and augmented the contractile response to 5‐HT, but in most cases indomethacin was without effect. 5 In endothelium‐intact tissues precontracted with uridine 5′‐triphosphate (UTP; 100 μ m ), 5‐HT did not evoke relaxation but rather caused further contraction. Under the same conditions acetylcholine (0.01–10 μ m ) evoked endothelium‐dependent relaxation. 6 These data demonstrate that the endothelium profoundly depresses contractions of rabbit isolated basilar artery to 5‐HT, and that this phenomenon can be fully accounted for by the release of an l ‐NOARG‐sensitive relaxing factor. Neither glibenclamide‐sensitive EDHF nor cyclo‐oxygenase products plays a major role. As we could find no evidence that 5‐HT stimulates the production of EDRF per se , and l ‐NOARG caused endothelium‐dependent contraction and augmented contractions to other vasoconstrictor agents, it seems likely that a basal release of EDRF underlies this phenomenon.