Differential Regulation of Renal Angiotensin Subtype AT^1A 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 AT² 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 AT² receptor was localized mainly to the glomeruli. The AT^1A but not AT² 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 rats, the AT^1A receptor was significantly reduced in ischemic and contralateral kidneys compared with sham-operated control rats. Reduction in AT² 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 AT² receptor protein is downregulated in rats with Ang II-induced hypertension. In renal hypertensive rats, the AT^1A receptor is bilaterally downregulated and the AT² receptor is downregulated only in the ischemic kidney. (Hypertension. 1999;33:96-101.).