PERINATAL ANG-II PROGRAMS ADULT-BLOOD PRESSURE, GLOMERULAR NUMBER, AND RENAL-FUNCTION IN RATS

ANG IT is known to be important in normal renal development, but the l ong-term consequences of a suppressed renin-angiotensin system (RAS) d uring the developmental period are not completely understood. This stu dy tested the hypothesis that the RAS in the developing animal is impo rtant in long-term regulation of renal function and arterial pressure. Newborn Sprague-Dawley rat pups were given the ANG II AT(1) receptor. antagonist losartan (25 mg . kg(-1) . day(-1) sc) for the first 12 da ys of postnatal life (Los). Body weights at weaning (22 days) were sig nificantly reduced in Los (53.4 +/- 3.2 vs. 64.5 +/- 3.6 g in controls ); however, at the time of study (similar to 22 wk), body weights and the kidney-to-body weight ratios were not different. In chronically in strumented conscious animals, glomerular filtration rate and effective renal plasma flow were reduced by 27 and 20%, respectively, in Los; t he filtration fraction was not different. Maximal urine concentrating ability was also reduced in Los (1,351 +/- 45 vs. 2,393 +/- 52 mosmol/ kg in controls). Mean arterial pressure was significantly higher in Lo s (134 +/- 3 vs. 120 +/- 1 mmHg). The number of glomeruli per kidney w as reduced by 42% in Los, but the total glomerular volume was unchange d. Thus perinatal blockade of ANG II ATI receptors results in fewer bu t enlarged glomeruli, reduced renal function, and an increased arteria l pressure in adulthood. These data indicate that perinatal ANG II, ac ting via AT1 receptors, plays an important role in renal development a nd long-term control of renal function and arterial pressure. Physiolo gical conditions that cause suppression of the RAS in the developing a nimal may have long-term consequences for renal function and blood pre ssure.