Perinatal ANG II programs adult blood pressure, glomerular number, and renal function in rats.

Abstract

ANG II is known to be important in normal renal development, but the long-term consequences of a suppressed renin-angiotensin system (RAS) during the developmental period are not completely understood. This study tested the hypothesis that the RAS in the developing animal is important in long-term regulation of renal function and arterial pressure. Newborn Sprague-Dawley rat pups were given the ANG II AT1 receptor antagonist losartan (25 mg . kg-1 . day-1 sc) for the first 12 days of postnatal life (Los). Body weights at weaning (22 days) were significantly reduced in Los (53.4 +/- 3.2 vs. 64.5 +/- 3.6 g in controls); however, at the time of study (approximately 22 wk), body weights and the kidney-to-body weight ratios were not different. In chronically instrumented conscious animals, glomerular filtration rate and effective renal plasma flow were reduced by 27 and 20%, respectively, in Los; the 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 Los (134 +/- 3 vs. 120 +/- 1 mmHg). The number of glomeruli per kidney was reduced by 42% in Los, but the total glomerular volume was unchanged. Thus perinatal blockade of ANG II AT1 receptors results in fewer but enlarged glomeruli, reduced renal function, and an increased arterial pressure in adulthood. These data indicate that perinatal ANG II, acting via AT1 receptors, plays an important role in renal development and long-term control of renal function and arterial pressure. Physiological conditions that cause suppression of the RAS in the developing animal may have long-term consequences for renal function and blood pressure.