MODULATION OF ANG-II RECEPTOR AND ITS MESSENGER-RNA IN NORMAL RAT BY LOW-PROTEIN FEEDING

Low-protein feeding results in reduced plasma renin activity (PRA), low prostaglandin production, high intra-renal vascular resistance, and reduced renal plasma flow (RPF) and glomerular filtration rate (GFR) in normal, intact rats. The hemodynamic changes are reversed by converting enzyme inhibitors. In this study, normal rats were fed normal protein (NP) or low protein (LP). PRA was 10.1 +/- 1.3 for NP vs. 5.1 +/- 1.7 ng . ml-1 . h-1 for LP (P < 0.001). Mean arterial pressure fell in both LP and NP during treatment with losartan (DuP-753, a specific angiotensin AT1-receptor inhibitor), but GFR and RPF in LP + losartan became indistinguishable from values obtained in NP and NP + losartan rats. Plasma Na and K and urine excretions of these two electrolytes were unchanged. Angiotensin II (ANG II) binding to isolated glomeruli (n = 19) revealed a dissociation constant of 1.11 +/- 0.22 vs. 1.22 +/- 0.20 nM (not significant) and maximal binding of 763 +/- 89 vs. 432 +/- 75 fmol/mg protein (P < 0.001), indicating an increased number of receptors without changes in affinity in LP. An increased number of receptors in LP compared with NP was also observed by quantitative autoradiography. These results reflect a predominant intrarenal alteration in the response to ANG II in LP. Northern blot and in situ hybridization analysis of the AT1 receptor mRNA showed enhanced gene expression in cortex (glomeruli) and medulla in LP. Dietary protein is an important modulator of the intrarenal actions of ANG II. We show for the first time that protein in the diet modulates the expression of the AT1 receptor gene and that ANG II mediates the hemodynamic changes of LP feeding through the AT1 receptor.