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Mechanism of prolonged vasorelaxation to ATP in the rat isolated mesenteric arterial bed
Author(s) -
Ralevic Vera
Publication year - 2001
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 - 10.1038/sj.bjp.0703868
Subject(s) - ouabain , methoxamine , chemistry , glibenclamide , endocrinology , medicine , suramin , muscle relaxation , vasodilation , contraction (grammar) , pharmacology , agonist , biochemistry , receptor , sodium , organic chemistry , diabetes mellitus
This study investigated the mechanism of prolonged relaxation to ATP in the rat isolated perfused mesenteric arterial bed. In methoxamine pre‐constricted preparations, ATP elicited dose‐dependent, endothelium‐dependent, rapid relaxation at 5 pmol – 0.05 μmol (R max 76±5.6%, pD 2 9.2±0.2), and contraction, followed by prolonged endothelium‐independent vasorelaxation at 0.05, 0.5 and 5 μmol (56±3.0, 87±2.9 and 85±4.6%). Suramin (100 μ M ), attenuated rapid (pD 2 7.8±0.1) and prolonged relaxation to ATP. The selective P2 receptor antagonist PPADS (10 μ M ) reduced prolonged, but not rapid relaxation. Neither phase of relaxation was affected by 8‐sulphophenyltheophylline (1 μ M ) or indomethacin (10 μ M ). α,β‐methylene ATP (α,β‐meATP; 10 μ M ) attenuated prolonged relaxation to ATP (relaxations at 0.05 and 0.5 μmol were 25±8.3 and 48±9.0%, respectively). α,β‐meATP blocked contractions and revealed rapid relaxation to ATP at 0.05 – 5 μmol. Capsaicin pre‐treatment did not affect either phase of vasorelaxation to ATP. α,β‐meATP (10 μ M ) had no effect on vasorelaxation mediated by electrical stimulation of capsaicin‐sensitive sensory nerves. High K + (25 m M ) attenuated prolonged relaxation to ATP (21±2.6 and 64±5.8%, at 0.05 and 0.5 μmol, respectively), but had no effect on rapid relaxation. Ouabain (1 m M ), an inhibitor of Na + /K + ‐ATPase, and glibenclamide (10 μ M ), an inhibitor of K ATP channels, also attenuated prolonged relaxation to ATP. Charybdotoxin (100 n M ), a selective inhibitor of K Ca channels, and tetraethylammonium (10 m M ) had no effect on rapid or prolonged relaxations. These results show that the prolonged phase of vasorelaxation to ATP in the rat isolated mesenteric arterial bed, which may be mediated by P2Y receptors, is endothelium‐independent, involves activation of Na + /K + ‐ATPase and K ATP channels, and is inhibited by α,β‐meATP. Neither prolonged nor rapid vasorelaxation to ATP involves capsaicin‐sensitive sensory nerves, adenosine P1 receptors, prostanoids or K Ca channels.British Journal of Pharmacology (2001) 132 , 685–692; doi: 10.1038/sj.bjp.0703868