REDUCTION OF THE HUMAN PLACENTAL VASCULAR RELAXATION TO PROGESTERONE BY GESTATIONAL DIABETES

Background: We have recently described a dose-dependent, endothelium-i ndependent relaxation to progesterone in human placental arteries and veins. This receptor-operated, cAMP-mediated relaxation may be of valu e in maintaining adequate blood flow in the placental circulation. Obj ective: To investigate if gestational diabetes alters this relaxation to progesterone. Study design: Isolated human placental vessels from p regnancies complicated by gestational diabetes and well matched contro ls (uncomplicated term pregnancies), incubated in Krebs-bicarbonate bu ffer and submaximally precontracted with KCI, were exposed to cumulati ve doses of progesterone (0.01-30 mu mol/liter), nitroglycerin (0.001- 1 mu mol/liter), arachidonic acid (0.01-10 mu mol/liter), forskolin (0 .01-10 mu mol/liter) and 5-hydroxytryptamine (serotonin, 0.01-10 mu mo l/liter). Results: The relaxation to progesterone in vessels from pati ents with gestational diabetes was reduced by 50-100% in both arteries and veins compared with control (for example, relaxation to 10 mu mol /liter progesterone was reduced from 52 +/- 7 to 18.8 +/- 5.4% in arte ries and from 58 +/- 8 to 19 +/- 5.2% in veins, n = 7-13, P < 0.05), w hereas responses to the other vasoactive agents were unchanged. Conclu sion: Based on these results, gestational diabetes significantly reduc es the relaxation to progesterone in human placental vessels. This alt eration of the relaxation to progesterone may lead to an increase in p lacental vascular resistance and possibly to a reduction of placental blood flow.