CAPTOPRIL NORMALIZES SYSTOLIC BLOOD-PRESSURE IN RATS WITH HYPERTENSION INDUCED BY FETAL EXPOSURE TO MATERNAL LOW-PROTEIN DIETS

Recent studies have demonstrated that the feeding of low protein diets to rats during pregnancy induces hypertension in their offspring. Mat ernal-diet-induced hypertension has been previously associated with el evated pulmonary angiotensin converting enzyme (ACE) activity. In the present study, the importance of the renin angiotensin system, and in particular ACE, in the maintenance of the hypertensive state, is inves tigated. Pulmonary and plasma ACE activity were determined in rats of different ages, following in utero exposure to 18 (control) or 9% (def icient) casein diets. No maternal diet induced changes in pulmonary AC E were noted, but at 4 and 13 weeks of age, plasma ACE activity was in creased by 34 and 134%, respectively in 9% casein exposed rats relativ e to controls (P < 0.001). Thirteen-week-old rats had significantly ra ised systolic blood pressure (28 mmHg, P < 0.05), and tended to have h igher diastolic blood pressure (not significant). These hypertensive a nimals had slightly raised plasma angiotensin II concentrations (30% h igher, not significant), but similar renin activities, when compared w ith normotensive controls. Treatment of normotensive and hypertensive rats with the ACE inhibitor captopril demonstrated that higher plasma ACE activity may play a major role in the maintenance of maternal-diet -induced hypertension. Whilst normotensive rats showed no significant response to drug treatment, systolic blood pressure in the hypertensiv e rats fell rapidly to the level observed in the normotensive control group. Blood pressure remained at this lower level until treatment was withdrawn, at which time pressure began to increase slowly, but stead ily. A period of 7-8 weeks was required following cessation of captopr il administration for the restoration of hypertension. The data are co nsistent with the hypothesis that components of the renin-angiotensin system, and in particular plasma ACE, are involved in the maintenance of maternal-diet-induced hypertension.