Endothelium-dependent vasodilator effects of platelet activating factor on rat resistance vessels

Abstract

To elucidate the mechanisms of the powerful and long-lasting hypotension produced by platelet activating factor (PAF), its effects on perfusion pressure in the perfused mesenteric arterial bed of the rat were examined. Infusion of PAF (10-11 to 3 x 10-10 M; EC50 = 4.0 x 10-11 M; 95% CL = 1.6 x 10-11 - 9.4 x 10-11 M) and acetylcholine (ACh) (10-10 to 10-6 M; EC50 = 3.0 ± 0.1 x 10-9 M) produced marked concentration-dependent vasodilatations which were significantly inhibited by treatment with detergents (0.1% Triton X-100 for 30 s or 0.3% CHAPS for 90 s). Pretreatment with CV-6209, a PAF antagonist, inhibited PAF- but not ACh-induced vasodilatation. Treatment with indomethacin (10-6 M) had no effect on PAF- or ACh-induced vasodilatation. These results demonstrate that extremely low concentrations of PAF produce vasodilatation of resistance vessels through the release of endothelium-derived relaxing factor (EDRF). This may account for the strong hypotension produced by PAF in vivo.