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

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 ) Ca 2+ were performed by confocal microscopy. PAF, at a concentration of 1 μ M , and the selective ET B agonists, IRL‐1620 and sarafotoxin S6C (100 n M ), 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 n M ) induced a significant concentration‐dependent nifedipine‐insensitive increase in tension and [Ca] i in both arteries and veins. Those responses to endothelin‐1 were significantly reduced by the ET A receptor antagonist, BQ‐123 (10 −6   M ), on both types of vessels, whereas the selective ET B receptor antagonist, BQ‐788, inhibited only the venous responses. The mixed ET A /ET B 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 ET A or ET B blockade without further affecting [Ca] i . PAF and the selective ET B agonists IRL‐1620, induced a sustained increase of [Ca] c and [Ca] n solely in venous cells and ET‐1 in both arterial and venous smooth muscle cells. 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.British Journal of Pharmacology (2002) 135 , 433–443; doi: 10.1038/sj.bjp.0704441