Importance of angiogenic action of angiotensin II in the glomerular growth of maturing kidneys

Abstract

We studied the effect of three antihypertensive drugs on the growth of glomeruli in four- to five-week-old Munich-Wistar rats (N = 24), which were undergoing rapid maturation processes. Young rats were given an angiotensin converting enzyme inhibitor (ACEI, enalapril, 50 mg/liter drinking water), verapamil (50 mg/liter) or hydralazine (80 mg/liter) or no treatment for six weeks. Body weight increased comparably in the treatment groups and age-matched controls, reaching on average 197 ± 11, 214 ± 12 and 198 ± 3 g in ACEI-, verapamil- and hydralazine-treated rats, respectively, versus 218 ± 6 g in control rats. Glomerular hemodynamic patterns, including glomerular capillary pressure, measured in maturing rats after one and six weeks of ACEI treatment were unaffected by ACEI. Mean planar area of glomeruli (PAmean) achieved was smaller than control in ACEI rats (6.60 ± 0.20 × 10-3mm2 vs. 5.37 ± 0.22, respectively, P < 0.005), but not in rats treated with other antihypertensive drugs. Furthermore, the maturational PAmean increase in rats given ACEI for six weeks was, on average, only half of that achieved by age-matched controls not given ACEI, in contrast to normal maturational growth with hydralazine or verapamil (29% increase in PAmean from normal baseline in ACEI vs. 52%, 53% and 59% increases in verapamil, hydralazine and control, respectively). In contrast, comparable PAmean values were found in adults with (7.08 ± 0.22 × 10-3mm2, N = 6) and without (6.98 ± 0.33 × 10-3mm2, N = 6) ACEI treatment given for six weeks. Therefore, ACEI, but not verapamil and hydralazine, causes growth retardation in maturing glomeruli. The studies suggest that the rapid growth of glomeruli in maturing kidneys is dependent upon the angiogenic effect of angiotensin II.