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.
Radenković
Miroslav
M
Department of Pharmacology, Clinical Pharmacology and Toxicology, Medical Faculty, University of Belgrade, PO Box 38, 11129 Belgrade, Serbia. miroslavr@beotel.net
Radunović
Nebojsa
N
Momcilov
Paja
P
Grbović
Leposava
L
D016640:Diabetes, Gestational / Q000503:physiopathology*; D004347:Drug Interactions; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008719:Methiothepin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011247:Pregnancy; D012701:Serotonin / Q000494:pharmacology* / Q000502:physiology*; D014469:Umbilical Arteries / Q000187:drug effects / Q000502:physiology*
D019335:Nitroarginine; D012701:Serotonin; D008719:Methiothepin; D010042:Ouabain; D007650:Ketanserin; D009543:Nifedipine; D005905:Glyburide