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 microns 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 NG-nitro-L-arginine or indomethacin. By contrast, bradykinin failed to relax vessels that had been preconstricted with potassium gluconate. In the combined presence of NG-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.
Pascoal
I F
IF
Department of Medicine, University of Chicago (III) 60637, USA.
Umans
J G
JG
D000109:Acetylcholine / Q000494:pharmacology*; D000328:Adult; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000378:metabolism; D019335:Nitroarginine; D009852:Omentum / Q000098:blood supply*; D011247:Pregnancy
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000109:Acetylcholine; D001920:Bradykinin; D007213:Indomethacin