Altered response of human umbilical artery to 5-HT in gestational diabetic pregnancy.

The aim of this investigation was to evaluate serotonin (5-HT) action on isolated human umbilical arteries (HUA) from normal and gestational diabetes mellitus (GDM) pregnancies. 5-HT caused HUA contraction in a concentration-dependent manner in both investigated groups but with lower efficacy in GDM. After endothelial denudation or in the presence of indomethacin (cyclooxygenase inhibitor), the 5-HT-evoked response was comparably augmented, but only in arteries from uncomplicated pregnancies. 5-HT contractions were unchanged by L-NOARG (NO-synthase inhibitor) or glibenclamide (K(ATP) channel blocker) in both investigated groups. Whereas nifedipine (Ca(2+) channel blocker) reduced the contractile effect of 5-HT and was more potent in GDM, ouabain (Na(+)/K(+)-ATPase inhibitor) caused the contraction of HUA prior to 5-HT addition in both groups, but with a significantly reduced effect in GDM. In vascular rings from GDM, methiothepin (a 5-HT(1)/5-HT(2) receptor antagonist) significantly reduced 5-HT-induced contraction to a similar extent as compared to uncomplicated pregnancies. Ketanserin (a 5-HT(2A) receptor antagonist) produced a concentration-dependent inhibition of the 5-HT effect in GDM. In conclusion, in normal pregnancies, 5-HT produced a concentration- and endothelium-dependent contraction of HUA, most probably via endothelial prostacyclin. In contrast, the contractile effect of 5-HT in GDM was reduced with apparent endothelial dysfunction. In both normal and diabetic pregnancies, voltage-gated Ca(2+) channels and Na(+)/K(+)-ATPase contribute to the 5-HT-evoked contraction, as well to the regulation of basal vascular tone, but those actions were notably impaired in GDM. In uncomplicated and diabetic pregnancies, the transduction mechanism of 5-HT involves activation of mixed population of 5-HT(1) and 5-HT(2A) receptors in the HUA.

Pharmacological evaluation of bradykinin effect on human umbilical artery in normal, hypertensive and diabetic pregnancy.

The objective of this investigation was to compare bradykinin (BK) action on isolated intact or denuded human umbilical artery (HUA) in normal pregnancy, pregnancy-induced hypertension (PIH) and gestational diabetes mellitus (GDM). Bradykinin contracted HUA in a concentration-dependent manner in all investigated groups. Control BK contractions were unchanged by L-NOARG (NO-synthase inhibitor), glibenclamide (K(ATP) channel blocker), or des-Arg(9)(leu(8))-BK (B(1) antagonist), while were reduced by indomethacin (cyclooxygenase inhibitior) or nifedipine (Ca(2+) channel blocker). After endothelial denudation in GDM, concentration-response curve for BK was shifted to the left in relation to control HUA from normal pregnancy. OKY-046 (thromboxane A(2) -synthase inhibitor) displaced concentration-response curve for BK to the right in PIH, whereas reduction in maximal contraction was obtained in HUA from GDM. Ouabain (Na(+)/K(+)-ATPase inhibitor) contracted HUA prior to BK addition in all groups. Apamin (small conductance K(Ca) channel blocker), TEA (non-selectve K(+) channel blocker) or Ba(++) (K(IR)(+) channel blocker) augmented maximal BK contractions in normal pregnancy, PIH and GDM, respectively. HOE 140 (B(2) antagonist) produced concentration-dependent inhibition of BK effect in all groups. Collectively, in HUA from all groups BK evoked vasoconstriction via smooth muscle B(2) receptors. Intact endothelium provided additional modulation of BK contraction in GDM. Contribution of contractile cyclooxygenase products to BK action was demonstrated, and in PIH and GDM thromboxane A(2) was also involved. Voltage-gated Ca(2+) channels and Na(+)/K(+)-ATPase contribute to the BK contraction, and to the regulation of basal vascular tone, respectively. Diverse K(+) channels modulate BK contraction in HUA by preventing excessive vasoconstriction.