Effects of diazoxide on maternal and fetal circulations in normotensive and hypertensive pregnant sheep.
Diazoxide is a potent antihypertensive agent due to its peripheral vasodilator action. For this reason it is used in the management of hypertensive crises in pregnancy. To assess the effects of an intravenous bolus injection of diazoxide on maternal and fetal hemodynamics an experimental study was performed in 11 chronically instrumented pregnant sheep. In six ewes hypertension was induced by surgical removal of one kidney and reduction of arterial blood flow to the remaining kidney (one-kidney renovascular hypertension). The other five ewes remained normotensive. In a second operation, one week after the first one, the animals were equipped with electromagnetic flow transducers and catheters for monitoring of blood flow in a renal, a uterine, and an umbilical artery and for measurement of maternal and fetal arterial blood pressures, and blood sampling. Maternal heart rate was derived from the arterial pressure curve, fetal heart rate from a fetal ECG. Experiments were begun on the third day after the second operation. In each experiment a bolus of 300 mg of diazoxide was administered intravenously, with or without rapid simultaneous infusion of 500 ml of a plasma expander. A total of 17 experiments were performed in the one-kidney hypertensive ewes (Group H), nine with and eight without plasma expander. In the five normotensive animals (Group NH) 10 experiments were done, four with and six without plasma expansion. During the control periods maternal arterial pressure was approximately 30 mm Hg higher in Group H than in Group NH. In Group H also maternal heart rate, and renal and uterine vascular resistances were significantly elevated. All fetal variables were equal in both groups. Administration of diazoxide without simultaneous plasma expansion resulted in both groups in a significant fall in maternal arterial pressure, a rise in maternal heart rate, and a fall in uterine and renal blood flows with a rise in vascular resistance. Fetal arterial pressure and umbilical blood flow showed no significant changes, but fetal heart rate showed a transient fall together with a drop in fetal pO2 and pH, although acidosis did not occur. When diazoxide was combined with a plasma expander maternal blood pressure did not change significantly in Group NH, but fell in Group H. Maternal heart rate rose significantly in both groups. The decrease in uterine and renal blood flows which occurred when diazoxide was given without plasma expansion was not observed.(ABSTRACT TRUNCATED AT 400 WORDS)
D000818:Animals; D001775:Blood Circulation / Q000187:drug effects; D003981:Diazoxide / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects*; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D010952:Plasma Substitutes / Q000494:pharmacology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy / Q000503:physiopathology*; D011270:Pregnancy, Animal / Q000187:drug effects; D012756:Sheep
D010952:Plasma Substitutes; D003981:Diazoxide