Adriamycin-related hypertension in pregnant rats: response to a thromboxane receptor antagonist.
1. In previous works we have described the development of hypertension and aggravation of proteinuria in rats who became pregnant after the administration of Adriamycin. This was associated with an increase in the glomerular thromboxane B2-prostaglandin E2 ratio. 2. To assess the pathogenetic role of thromboxane in this model, female Wistar rats were mated 2 weeks after receiving Adriamycin (3.5 mg/kg intravenously). Rats were then treated with the thromboxane-receptor antagonist daltroban, 60 mg day-1 kg-1 orally, beginning on day 11 of pregnancy. Systolic blood pressure, proteinuria and the urinary excretion of thromboxane B2, 6-keto-prostaglandin F1 alpha and prostaglandin E2 were measured serially before mating, and on days 14 and 21 of pregnancy. The results were compared with those in Adriamycin-(treated) pregnant rats not treated with daltroban, Adriamycin-treated virgin rats and normal virgin or pregnant rats either treated or untreated with daltroban. 3. In daltroban-treated pregnant and virgin rats treated with Adriamycin, systolic blood pressure remained normal, whereas it increased significantly (P < 0.05) in untreated animals. On day 14, blood pressure was higher in non-daltroban-treated Adriamycin-treated pregnant rats than in non-daltroban-treated Adriamycin-treated virgin rats. Treatment had no effect on blood pressure in normal virgin or pregnant rats. Proteinuria was higher in pregnant rats treated with Adriamycin than in Adriamycin-treated virgin rats, but it was not reduced by daltroban.(ABSTRACT TRUNCATED AT 250 WORDS)
Rathaus
M
M
Department of Nephrology, Meir Hospital, Kfar Saba, Israel.
Podjarny
E
E
Pomeranz
A
A
Green
J
J
Bernheim
J
J
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D004195:Disease Models, Animal; D004317:Doxorubicin; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000652:urine; D010648:Phenylacetates / Q000627:therapeutic use*; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000627:therapeutic use*; D013929:Thromboxane B2 / Q000652:urine; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D010648:Phenylacetates; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D013931:Thromboxanes; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D004317:Doxorubicin; C051762:daltroban