(Hypertension. 1999;33:340-346.)
© 1999 American Heart Association, Inc.
Scientific Contributions |
Regulation of Angiotensin II Type 1 Receptor mRNA and Protein in Angiotensin II–Induced Hypertension
From the Departments of Physiology (L.M.H.-B., D.F.O., L.G.N.) and Pediatrics (S.S.E.-D.), Tulane University School of Medicine, New Orleans, La.
Correspondence to Lisa M. Harrison-Bernard, PhD, Department of Physiology SL39, Tulane University School of Medicine, 1430 Tulane Ave, New Orleans, LA 70112-2699. E-mail lharris{at}mailhost.tcs.tulane.edu
Abstract—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 AT1A- 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 AT1A/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, AT1A/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.
Key Words: kidney • liver • adrenal gland • gene expression • antibodies
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