Regulation of angiotensin II type 1 receptor mRNA and protein in angiotensin II-induced hypertension

Chronic elevations of circulating angiotensin II (Ang II) cause sustained hypertension and enhanced accumulation of intrarenal Ang II by an AT₁ receptor-dependent process. The present study tested the hypothesis that chronic elevations in circulating Ang II regulate AT₁ 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<0.05). Semiquantitative reverse transcription polymerase chain reaction using rat AT(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<0.05). Western blot analysis showed that AT₁ protein levels in the kidney and liver were also similar in the two groups. Therefore, these results indicate that renal and liver AT₁ receptor gene expression is maintained in Ang II- induced hypertension. The failure to downregulate AT₁ receptor mRNA and protein levels thus allows the sustained effects of chronic elevations in Ang II to elicit progressive increases in arterial pressure.