ROLE OF R-TYPE CALCIUM CHANNELS IN THE RESPONSE OF THE PERFUSED ARTERIAL AND VENOUS MESENTERIC VASCULATURE OF THE RAT TO PLATELET-ACTIVATING-FACTOR

1 The vasoactive properties of platelet-activating factor (PAF) were s tudied in the arterial and venous vasculature of the rat double-perfus ed mesenteric bed. Although PAF (0.01-0.3 pmol) induced a dose-depende nt 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-arg inine methyl ester (L-NAME, 100 mu M), a nitric oxide synthase inhibit or, markedly reduced the vasodilatation induced by PAF in the arterial mesenteric vasculature and potentiated the contractile responses of t he venous side to the same agent. 3 The PAF antagonist, WEB-2170, mark edly reduced the response to PAF on both sides of the mesenteric vascu lature. However, the IC50 of WEB-2170 against PAF was reached at a muc h higher concentration (1 x 10(-8) M) on the arterial side than on the venous side (5.3 x 10(-11) M), Furthermore, a second antagonist of PA F receptors, SRI-63441, although being less potent on the venous vascu lature than WEB-2170, was equipotent in antagonizing the venoconstrict ion and the arterial dilatation induced by PAF (IC50 of SRI-63441, art erial side: 2.9 x 10(-9) M; venous side: 3.1 x 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-i nduced vasoactive properties on both sides of the mesenteric vasculatu re. 5 Our results illustrate the differential vasoactive properties of PAF in the mesenteric vasculature of the rat. These vasoactive respon ses occur following activation of specific receptors for PAF or, alter natively, through activation of R-type calcium channels.