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

Miroslav Radenković, Leposava Grbović, Nebojsa Radunović, Paja Momcilov
Pharmacological Reports  
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
more » ... 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.
pmid:17377208 fatcat:uu7upkudz5gbhjku44zxvhn4ie