Differential regulation of renal angiotensin subtype AT1A and AT2 receptor protein in rats with angiotensin-dependent hypertension

This study was designed to investigate distribution and regulation of the renal AT(1A) and AT(2) subtype receptors in rats with either systemic angiotensin II (Ang II)-induced hypertension or acute phase renal hypertension (2-kidney, 1-clip [2K1C] or 2-kidney, 1-figure-of-8-wrap [2K1W]). In normal rat kidneys, positive immunostaining for the AT(1A) receptor was observed in the intrarenal vasculature, glomeruli, proximal and distal tubules, and collecting ducts. The AT(2) receptor was localized mainly to the glomeruli. The AT(1A) but not AT(2) receptor protein expression was significantly reduced in rats with 10-day systemic Ang II-induced hypertension. In both 7-day 2K1C and 3-day 2K1W mts, the AT(1A) receptor was significantly reduced in ischemic and contralateral kidneys compared with sham-operated control rats. Reduction in AT(2) receptor expression was observed only in the ischemic kidneys in 2K1C and 2K1W renal hypertensive rats. These results demonstrate that the AT(1A) receptor is widely distributed in the glomerulus and all other nephron segments of the rat kidney. Renal AT(1A) but not AT(2) receptor protein is downregulated in rats with Ang II-induced hypertension. In renal hypertensive rats, the AT(1A) receptor is bilaterally downregulated and the AT(2) receptor is downregulated only in the ischemic kidney.