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Role of R‐type calcium channels in the response of the perfused arterial and venous mesenteric vasculature of the rat to platelet‐activating factor
Author(s) -
Claing Audrey,
Bkaily Ghassan,
Berthiaume Nathalie,
Sirois Pierre,
RolaPleszczynski Marek,
D'OrléansJuste Pedro
Publication year - 1994
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.1476-5381.1994.tb13211.x
Subject(s) - bradykinin , vasodilation , platelet activating factor , isradipine , mesenteric arteries , medicine , endocrinology , vasoconstriction , nifedipine , anesthesia , chemistry , calcium , antagonist , artery , receptor
1 The vasoactive properties of platelet‐activating factor (PAF) were studied in the arterial and venous vasculature of the rat double‐perfused mesenteric bed. Although PAF (0.01–0.3 pmol) induced a dose‐dependent vasodilatation of the arterial mesenteric vasculature, it triggered only vasoconstrictions on the venous side, with an intact endothelium as bradykinin induced a significant venodilatation. 2 N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME, 100 μ m ), a nitric oxide synthase inhibitor, markedly reduced the vasodilatation induced by PAF in the arterial mesenteric vasculature and potentiated the contractile responses of the venous side to the same agent. 3 The PAF antagonist, WEB‐2170, markedly reduced the response to PAF on both sides of the mesenteric vasculature. However, the IC 50 of WEB‐2170 against PAF was reached at a much higher concentration (1 × 10 −8 M) on the arterial side than on the venous side (5.3 × 10 −11 M). Furthermore, a second antagonist of PAF receptors, SRI‐63441, although being less potent on the venous vasculature than WEB‐2170, was equipotent in antagonizing the venoconstriction and the arterial dilatation induced by PAF (IC 50 of SRI‐63441, arterial side: 2.9 × 10 −9 M; venous side: 3.1 × 10 −9 M). 4 The dual L‐ and R‐calcium channel blocker, isradipine (PN 200–110), but not the L‐type calcium channel blocker, nifedipine, markedly reduced the PAF‐induced vasoactive properties on both sides of the mesenteric vasculature. 5 Our results illustrate the differential vasoactive properties of PAF in the mesenteric vasculature of the rat. These vasoactive responses occur following activation of specific receptors for PAF or, alternatively, through activation of R‐type calcium channels.