PREGNANCY-INDUCED HYPERTENSION IN RATS WITH EARLY ADRIAMYCIN NEPHROPATHY

In up to 60% of women with chronic renal disease an elevation of blood pressure is seen during pregnancy. The pathogenesis of this complicat ion may be related to a diminished synthesis of vasodilatory substance s by endothelial cells and to an increased sensitivity to vasopressor hormones such as angiotensin II. Previous experimental studies in rats with early chronic renal disease (adriamycin nephropathy, AN) have sh own that this pregnancy-induced hypertension is associated with a lowe red synthesis of glomerular PGE2. In the present study the vascular re sponse to vasoactive substances was evaluated. In AN rats the sensitiv ity to an acute infusion of angiotensin II was augmented, whilst it wa s blunted in normal pregnant rats. Chronic treatment with the thrombox ane-(Tx)-receptor antagonist, daltroban (60 mg/kg/day, p.o.) administe red from midpregnancy induced a similar reduction in blood pressure in both AN virgin and pregnant rats. This suggests that adriamycin per s e may induce vascular damage which may interfere with the normal vascu lar adaptation to pregnancy. Stimulation of NO synthesis with L-argini ne decreased MAP values significantly in PAN rats but did not modify t hem during normal pregnancy. In additional experimental inhibition of the endothelial-derived relaxing factor (EDRF), nitric oxide (NO) synt hesis with NAME from midpregnancy significantly increased SBP and MAP in normal rats. By contrast, in PAN rats chronic NAME treatment had no effect. In summary, the development of hypertension in pregnant rats with AN may be associated to endothelial cell dysfunction. This lesion may on the one hand decrease the synthesis of vasodilator hormones (p rostaglandins, nitric oxide) whilst on the other it may lead to an aug mented sensitivity to vasopressor hormones (thromboxane and angiotensi n II).