Distinct mechanisms of modulation of angiotensin II type I receptor gene expression in heart and aorta
Wang, D.H.; Yao, A.; Zhao, H.; DiPette, D.J.
Hypertension 29(5): 1104-1108
1997
ISSN/ISBN: 0194-911X PMID: 9149673 Document Number: 474326
The purpose of the present study was to test the hypothesis that hypertension induced by reduced renal mass (RRM) upregulates gene expression of the type 1 angiotensin II (Ang II) receptor (AT-1) in the thoracic aorta and heart through an Ang II-dependent mechanism. Three groups of rats were given 1% NaCl water and subjected to RRM, RRM plus captopril (RRM+Cap, 30 mg/kg per day), or sham surgery. Tail-cuff systolic blood pressure was significantly elevated in RRM and RRM+Cap rats compared with sham-operated rats. The ratios of the medial wall area of the thoracic aorta and heart weight to body weight were significantly elevated in RRM and RRM+Cap rats compared with sham-operated rats. Northern blot analysis indicated that the ratio of AT-1 to GAPDH mRNA in the aorta was significantly higher in RRM (1.85 +- 0.52) compared with sham-operated (0.21 +- 0.04) and RRM+Cap (0.55 +- 0.20) rats. In contrast, the ratio of AT-1 to GAPDH mRNA in the heart was significantly increased in both RRM (1.09 +- 0.23) and RRM+Cap (1.00 +- 0.09) compared with sham-operated (0.34 +- 0.06) rats. Thus, RRM hypertension upregulates AT-1 mRNA expression in both the hypertrophied aorta and heart. Captopril treatment without altering blood pressure in RRM rats prevents the increase in AT-1 mRNA in the aorta but not the heart. These results suggest that different tissue-specific mechanisms of AT-1 gene regulation exist; ie, in aorta, an Ang II- or kinin-dependent mechanism is operant, whereas in heart, RRM-induced upregulation of AT-1 mRNA may be pressure dependent.