Nitric oxide-mediated vascular tone in the fetal placental circulation of patients with type 1 diabetes mellitus.
Endothelium-derived nitric oxide (NO) plays a key role in the regulation of vascular tone in health and disease. The present study addresses the contribution of NO to the baseline vascular tone in the fetal placental circulation of type 1 diabetic women. To this end, we performed ex-vivo dual perfusions of isolated cotyledons from seven women with type 1 diabetes mellitus and 24 healthy women. The fetal arterial pressure was considered to be a measure of fetal vascular resistance. The contribution of NO to the baseline vascular tone of the fetal placental circulation was quantified by addition of the NO-synthase inhibitor N(G)-nitro-arginine-methylester (L-NAME). Apart from the diabetic state, we studied the influence of exogenous insulin on the response to L-NAME. Mean (+/-SEM) baseline fetal arterial pressure was higher in diabetes (25.7+/-3.4 mm Hg vs 18.0+/-1.7 mm Hg, P<0.05). Maximum perfusion pressure after L-NAME was 87.9+/-7.1 mm Hg in diabetes vs 58.9+/-4.5 mm Hg in controls (P<0.01). The net L-NAME-induced increase in fetal arterial pressure was higher in diabetes (62.2+/-9.1 mm Hg vs 40.9+/-3.5 mm Hg, P<0.05). Although insulin induced a shift to the left of the L-NAME-curve, the net L-NAME-induced increase in fetal arterial pressure was not affected. We conclude that diabetes is associated with an increased baseline vascular tone of the fetal placental vascular bed. This can not be explained by attenuated NO-mediated effects. In contrast, the activity of the NO-pathway seems to be increased in diabetes. The latter observation seems not to be caused by high insulin levels.
Department of Pharmacology-Toxicology 233, University Medical Centre Nijmegen, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
T M
TM
Bisseling
A C
AC
Wouterse
E A
EA
Steegers
L
L
Elving
F G
FG
Russel
P
P
Smits
D000328:Adult; D001794:Blood Pressure / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D005260:Female; D005333:Fetus / Q000098:blood supply*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010920:Placenta / Q000098:blood supply* / Q000737:chemistry; D021041:Placental Circulation; D011247:Pregnancy; D015398:Signal Transduction
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester