Differential Regulation of Renal Angiotensin Subtype AT 1A and AT 2 Receptor Protein in Rats With Angiotensin-Dependent Hypertension

Abstract

Abstract —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 rats, 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.