The renin-angiotensin system and compensatory renal hypertrophy in the rat

Angiotensin II (Ang II) may act as an angiogenic and growth promoting factor in different tissues. To assess the role of Ang II in compensatory renal growth following unilateral nephrectomy (UNX), we measured renin, angiotensinogen, and Ang II type 1 (AT1) receptor mRNA levels, as well as Ang II receptor density, in two groups of Sprague-Dawley rats 7 days after either sham operation or UNX. Half of each group received either no treatment or an angiotensin-converting enzyme inhibitor (100 mg/dL captopril in the drinking water, initiated at the time of the intervention). Following UNX, the ratio of kidney weight to body weight (KW/BW) in untreated animals was greater than in rats undergoing sham UNX (0.46 +/- 0.01 v 0.37 +/- 0.01%, P < .01). Neither renal renin, nor renal or hepatic angiotensinogen mRNA levels, determined by slot blot hybridization, changed significantly after UNX. Ang II receptor density in glomeruli, determined using an 125I-Sar1-Ile8 Ang II in situ receptor binding assay on frozen kidney sections, did not change significantly after UNX, nor did renal AT1 receptor mRNA. In captopril-treated rats, KW/BW was greater in UNX than in sham operated rats (0.44 +/- 0.01 v 0.37 +/- 0.01%, P < .01), similar to results in untreated animals. Renal and hepatic angiotensinogen mRNA levels were not affected by captopril treatment and did not change further in response to UNX. Captopril treatment increased renin mRNA in both sham operated and UNX rats as compared with untreated controls, but had no significant effect on Ang II receptor density and AT1 receptor mRNA; and no change was observed in either variable as a consequence of UNX. Thus, compensatory renal hypertrophy following UNX occurred in the absence of measurable changes in components of the renin-angiotensin system, and despite functionally significant inhibition of this system by captopril. These data do not support a critical role for Ang II in compensatory renal hypertrophy.