Regulation of Angiotensin II Type 1 Receptor mRNA and Protein in Angiotensin II–Induced Hypertension

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Abstract
Abstract —Chronic elevations of circulating angiotensin II (Ang II) cause sustained hypertension and enhanced accumulation of intrarenal Ang II by an AT 1 receptor–dependent process. The present study tested the hypothesis that chronic elevations in circulating Ang II regulate AT 1 mRNA and protein expression in a tissue-specific manner. Sprague-Dawley rats were infused with Ang II (80 ng/min) or vehicle subcutaneously for 13 days via osmotic minipump. On day 12, systolic blood pressure averaged 186±12 mm Hg in Ang II–infused rats compared with rats given vehicle (121±2 mm Hg). Plasma renin activity was markedly suppressed in the Ang II–infused rats compared with vehicle-infused rats (0.1±0.01 versus 4.9±0.9 ng of Ang I · mL −1 · h −1 ; P 1A - and glyceraldehyde-3-phosphate-dehydrogenase (GAPDH)-specific primers was followed by Southern blot hybridization using specific radiolabeled cDNA or oligonucleotide probes. The results showed that the ratios of AT 1A /GAPDH mRNA in the kidney (0.19±0.05 versus 0.26±0.03) and liver (2.8±0.9 versus 3.0±0.5) were comparable in Ang II– and vehicle-infused rats. In contrast, AT 1A /GAPDH mRNA levels were increased in the adrenal glands of Ang II–infused rats (0.49±0.04 versus 0.36±0.02; P 1 protein levels in the kidney and liver were also similar in the two groups. Therefore, these results indicate that renal and liver AT 1 receptor gene expression is maintained in Ang II–induced hypertension. The failure to downregulate AT 1 receptor mRNA and protein levels thus allows the sustained effects of chronic elevations in Ang II to elicit progressive increases in arterial pressure.