Effect of pregnancy on mechanisms of relaxation in human omental microvessels

We assessed mechanisms of acetylcholine- and bradykinin-induced relaxations in human omental resistance vessels. Ring segments (approximately 200 mu m normalized ID) were dissected from omental biopsies obtained from women at laparotomy (nonpregnant) or at cesarean delivery (pregnant) and were studied under isometric conditions in a Mulvany-Halpern myograph. All arginine vasopressin-preconstricted vessels relaxed in a strictly endothelium-dependent manner to acetylcholine and bradykinin; maximal relaxations were not decreased by either N-G-nitro-L-arginine or indomethacin. By contrast, bradykinin failed to relax vessels that had been preconstricted with potassium gluconate. in the combined presence of N-G-nitro-L-arginine and indomethacin, addition of charybdotoxin, a selective antagonist of some calcium-sensitive potassium channels, did not inhibit maximal bradykinin-induced relaxation. By contrast, addition of 10 mmol/L tetraethylammonium chloride abolished relaxation in vessels from nonpregnant women but not in vessels from gravidas. We conclude that bradykinin relaxes these human resistance arteries in an endothelium-dependent but predominantly nitric oxide- and prostanoid-independent manner; relaxation likely depends on the action of an endothelium-derived hyperpolarizing vasodilator. Furthermore, in striking contrast to mechanistic insights from animal studies, human pregnancy appears to augment a mechanism of endothelium-dependent relaxation in these vessels that is insensitive to the inhibitors noted above, Whether a similar novel vasodilator mechanism in vivo contributes to the physiological vasodilation that characterizes human gestation or whether failure of such a mechanism might lead to preeclampsia remains the subject of future study.