EARLY ADMINISTRATION OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR CAPTOPRIL, PREVENTS THE DEVELOPMENT OF HYPERTENSION PROGRAMMED BY INTRAUTERINE EXPOSURE TO A MATERNAL LOW-PROTEIN DIET IN THE RAT

1. Associations of intrauterine exposure to maternal undernutrition wi th later hypertension and coronary heart disease in the human populati on have been duplicated in the rat. Fetal exposure to low protein diet s produces offspring that develop raised systolic blood pressure by th e age of weaning, This animal model of 'programmed' hypertension was u sed to investigate the role of the renin-angiotensin system in the ini tiation and maintenance of high blood pressure. 2. Pregnant rats were fed diets containing 18 or 9% casein from conception until littering. The offspring from these pregnancies were administered captopril eithe r between 2 and 4 weeks of age, or from 10 to 12 weeks of age. 3. The feeding of low protein diets in pregnancy had no effect upon the repro ductive ability of female rats and the offspring generated were of nor mal birthweight. By 4 weeks of age the male and female offspring of lo w-protein-fed dams had systolic blood pressures that mere 24-25 mmHg h igher than those of rats exposed to a control diet in utero, 4. Treatm ent of 10-week-old female offspring with captopril for 2 weeks indicat ed that angiotensin II formation may play a role in the maintenance of high blood pressure in low-protein-exposed rats. While captopril had no significant effect upon systolic pressures of rats exposed to the c ontrol diet in intrauterine life, the systolic blood pressures of low- protein animals rapidly declined by 31 mmHg, 5. Administration of capt opril to male and female offspring between 2 and 4 weeks of age exerte d longterm effects upon systolic blood pressure. Eight weeks after ces sation of treatment, at an age where maximal blood pressures are achie ved, captopril-treated, low-protein-exposed rats had similar blood pre ssures to normotensive rats exposed to the protein-replete diet in ute ro, 6. In conclusion, we hale demonstrated that the elevation of adult blood pressure associated with fetal exposure to a maternal low-prote in diet, is prevented by early administration of an angiotensin-conver ting enzyme inhibitor. The actions of angiotensin II in the late suckl ing period may be a critical determinant of long-term cardiovascular f unctions in these animals.