Comparison of relaxant effects of nifedipine and NS11021 on isolated umbilical arteries of healthy and preeclamptic pregnant women

Abstract

ObjectivesPotassium (K+) channel openers and calcium (Ca2+) channel blockers are currently used to treat acute severe hypertension in pregnancy. We aimed to investigate the vasorelaxant effect of NS11021, a potent and specific big-conductance Ca2+-activated K+ (BKCa) channel activator, and to compare it with the vasorelaxant effect of nifedipine on human umbilical arteries (HUAs) isolated from healthy and preeclamptic pregnants. Study designA total of 29 HUAs were isolated immediately after delivery from 14 healthy and 15 preeclamptic pregnant with severe features. The concentration-dependent relaxation responses were obtained to nifedipine and NS11021 on HUAs precontracted with endothelin-1 (ET-1) (10-8 M) in an isolated tissue bath. ResultsBoth nifedipine and NS11021 caused concentration-dependent relaxation responses in HUAs from healthy and preeclamptic pregnants. While the maximum responses (Emax) and pD2 values of nifedipine did not change significantly in both groups, the Emax and pD2 values of NS11021 were significantly decreased in the preeclampsia group (Emax ± SEM; %75.57 ± 4.53 and %43.75 ± 14.00 and pD2 ± SEM; 6.92 ± 0.26 and 5.24 ± 0.53 respectively, p < 0.05). In addition, the pD2 value of NS11021 was not significantly different from that of nifedipine in the control group, but decreased significantly in the preeclampsia group (pD2 ± SEM 7.1 ± 0.41 and 5.2 ± 0.53, p < 0.05, respectively). ConclusionsEfficacy and potency of NS11021 decreased in HUAs from preeclamptic pregnants. Also, NS11021 is less potent than nifedipine in the preeclampsia group. BKCa channels may have a role in the pathogenesis of preeclampsia, however, further experimental studies are needed to elucidate that.