Alterations in relaxation to lactate and H(2)O(2) in human placental vessels from gestational diabetic pregnancies.
We determined whether alterations in the mechanism of relaxation to H(2)O(2) potentially contribute to the enhanced prostaglandin-mediated contractile response to H(2)O(2) and posthypoxic reoxygenation seen in human placental vessels of pregnancies with gestational diabetes mellitus (GDM). Isolated placental arteries and veins from GDM and uncomplicated full-term pregnancies were precontracted with prostaglandin F(2alpha) (PO(2) 35-38 Torr) and then exposed to lactate (1-10 mM), arachidonic acid (0.01-10 microM), nitroglycerin (1 nM-1 microM), forskolin (0.01-10 microM), or H(2)O(2) (1 microM-1 mM + 10 microM indomethacin). The rates of tissue H(2)O(2) metabolism by catalase and nitrite production were measured. The relaxation to lactate was reduced in GDM placental arteries and veins by 54-85 and 66-80%, and the relaxation to H(2)O(2) was inhibited by 80-94% in GDM placental veins compared with vessels from uncomplicated full-term pregnancies. H(2)O(2) caused only minimal relaxation of placental arteries. Responses to other relaxing agents were not altered in the GDM placental vessels. Diabetic vessels showed rates of nitrite production that were increased by 113-195% and rates of H(2)O(2) metabolism by catalase that were decreased by 44-61%. The loss of relaxation to H(2)O(2) and lactate (mediated via H(2)O(2)), perhaps as a result of the inhibition of catalase by nitric oxide, may explain the previously reported enhancement of prostaglandin-mediated contractile responses to H(2)O(2) and posthypoxic reoxygenation seen in GDM placental vessels.
Figueroa
R
R
Department of Obstetrics and Gynecology, New York Medical College, Valhalla, New York 10595, USA.
Martinez
E
E
Fayngersh
R P
RP
Tejani
N
N
Mohazzab-H
K M
KM
Wolin
M S
MS
D000293:Adolescent; D000328:Adult; D016718:Arachidonic Acid; D005576:Colforsin / Q000494:pharmacology; D016640:Diabetes, Gestational / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D019344:Lactic Acid / Q000494:pharmacology*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000503:physiopathology; D009573:Nitrites / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology; D010920:Placenta / Q000098:blood supply*; D011247:Pregnancy
D009573:Nitrites; D005576:Colforsin; D016718:Arachidonic Acid; D019344:Lactic Acid; D006861:Hydrogen Peroxide; D005996:Nitroglycerin; D007213:Indomethacin