Increased acetylcholine-induced vasodilation in pregnant rats - A role forgap junctional communication

We have tested the hypothesis that increased gap junctional communication c ontributes to the augmented endothelium-dependent vasodilation in pregnancy . Contractile force and connexin43 expression were measured in aortic rings from nonpregnant and pregnant rats. Norepinephrine-constricted aortas from pregnant rats were more sensitive to acetylcholine, but not to sodium nitr oprusside, compared with those from nonpregnant rats. Vessels from pregnant rats, constricted either with 45 mmol/L KCl or with norepinephrine + 10(-4 ) mol/L N-G-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide sy nthase, also exhibited greater relaxation to acetylcholine. Heptanol, an un coupler of gap junctional communication, inhibited acetylcholine responses in norepinephrine-constricted aortas from nonpregnant rats but greatly impa ired acetylcholine relaxation in aortas from pregnant rats. Heptanol also i nhibited in both groups acetylcholine responses in vessels constricted with KCl, only minimally affected acetylcholine relaxation in arteries constric ted with norepinephrine + L-NMMA, and did not change sodium nitroprusside-i nduced relaxation. Tetraethylammonium chloride induced greater contractions in control aortas compared with aortas from pregnant rats. Increased conne xin43 mRNA levels were found in the uterus and in the mesenteric, uterine, and thoracic aortic arteries, but not in the heart and brain, from pregnant rats. These results suggest that increased gap junctional communication, p ossibly due to increased gap junction protein expression, may facilitate th e effects of endothelium-derived relaxing factors, contributing to the augm ented endothelium-dependent relaxation in arteries from pregnant rats.