Maintenance of renal AT1 receptor mRNA levels in angiotensin II - induced hypertension

Alterations in angiotensin (Ang) II type 1 (AT1) gene expression may be a mechanism by which tissue responsiveness to AngII is controlled. Previous studies indicate that chronic low dose AngII infusion increases intrarenal AngII levels via an AT1 receptor mediated event and suggest an important role of intrarenal AngII in the hypertensinogenic process. The present study was designed to test the hypothesis that chronic AngII infusion influences renal AT1A gene expression. Male Sprague-Dawley rats weighing 230±4g were infused with 80 ng/min AngII (n=5) or vehicle (n=5) via an osmotic minipump implanted subcutaneously for two weeks. Conscious systolic blood pressure measured on day 12 was elevated in AngII infused rats compared to vehicle (180±15 vs 120±5mmHg). As expected, plasma renin activity was markedly suppressed in the AngII infused rats (4.6±1.7 vs 0.09±0.01 ng AngI/ml/hr). Semiquantitative RT-PCR on total kidney RNA using AT1A specific primers was followed by Southern blot hybridization using an AT1A specific oligonucleotide. Densitometric analysis demonstrated no change in renal AT1A mRNA in AngII infused rats compared to vehicle (2.1±0.1 vs 2.3±0.1 d.u.). Therefore, these results indicate that renal AT1A receptor gene expression is not altered in AngII induced hypertension allowing the sustained effect of chronically elevated AngII on renal function.