Comparison of the contractile and calcium-increasing properties of platelet-activating factor and endothelin-1 in the rat mesenteric artery and vein

1 In the present study, the properties of endothelin-1 (ET-1) and platelet-activating factor (PAF) in inducing contraction and increased intracellular-free calcium level in rat mesenteric arteries and veins were studied. Furthermore, measurements of cytosolic ([Ca](c)) and nuclear ([Ca](n)) Ca2+ were performed by confocal microscopy. 2 PAF, at a concentration of 1 muM, and the selective ETB agonists, IRL-1620 and sarafotoxin S6C (100 nM), induced a marked constriction and increase in [Ca](i) in the mesenteric vein but not in the artery. On the other hand, endothelin-1 (1 - 100 nM) induced a significant concentration-dependent nifedipine-insensitive increase in tension and [Ca](i) in both arteries and veins. 3 Those responses to endothelin-1 were significantly reduced by the ETA receptor antagonist, BQ-123 (10(-6) M), on both types of vessels, whereas the selective ETB receptor antagonist, BQ-788, inhibited only the venous responses. The mixed ETA/ETB receptor antagonist, SB 209670, reduced the ET-1-induced venous responses to the same level of that found in presence of BQ-123 or BQ-788. However, concomitant applications of BQ-123 and BQ-788 reduced the vasoconstriction below to that induced by ETA or ETB blockade without further affecting [Ca](i). 4 PAF and the selective ETB agonists IRL-1620, induced a sustained increase of [Ca](c) and [Ca](n) solely in venous cells and ET-I in both arterial and venous smooth muscle cells. 5 Thus, PAF increases total intracellular calcium concentration and tension on the smooth muscle cells from venous origin only. Furthermore, ET-1-induced vasoactive as well as [Ca](i) and [Ca](n) increasing effects are mediated by distinct receptors on venous and arterial smooth muscles.