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 complication may be related to a diminished synthesis of vasodilatory substances 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 shown that this pregnancy-induced hypertension is associated with a lowered synthesis of glomerular PGE2. In the present study the vascular response to vasoactive substances was evaluated. In AN rats the sensitivity to an acute infusion of angiotensin II was augmented, whilst it was blunted in normal pregnant rats. Chronic treatment with the thromboxane-(Tx)-receptor antagonist, daltroban (60 mg/kg/day, p.o.) administered from mid-pregnancy induced a similar reduction in blood pressure in both AN virgin and pregnant rats. This suggests that adriamycin per se may induce vascular damage which may interfere with the normal vascular adaptation to pregnancy. Stimulation of NO synthesis with L-arginine decreased MAP values significantly in PAN rats but did not modify them during normal pregnancy. In additional experimental inhibition of the endothelial-derived relaxing factor (EDRF), nitric oxide (NO) synthesis with NAME from mid-pregnancy 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Bernheim
J
J
Department of Nephrology, Meir Hospital, Kfar Saba, Israel.
Podjarny
E
E
Pomeranz
A
A
Feldman
V
V
Gonen
O
O
Rathaus
M
M
D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004317:Doxorubicin; D005260:Female; D006973:Hypertension / Q000209:etiology*; D019331:NG-Nitroarginine Methyl Ester; D009401:Nephrosis / Q000139:chemically induced* / Q000150:complications* / Q000503:physiopathology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D010648:Phenylacetates / Q000494:pharmacology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000209:etiology*; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology
D010648:Phenylacetates; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D000804:Angiotensin II; D009569:Nitric Oxide; D004317:Doxorubicin; D001120:Arginine; C051762:daltroban; D019331:NG-Nitroarginine Methyl Ester