DISTINCT MECHANISMS OF MODULATION OF ANGIOTENSIN-II TYPE-I RECEPTOR GENE-EXPRESSION IN HEART AND AORTA

The purpose of the present study was to test the hypothesis that hyper tension induced by reduced renal mass (RRM) upregulates gene expressio n of the type 1 angiotensin II (Ang II) receptor (AT(1)) in the thorac ic aorta and heart through an Ang II-dependent mechanism. Three groups of rats were given 1% NaCl water and subjected to RRM, RRM plus capto pril (RRM+Cap, 30 mg/kg per day), or sham surgery. Tail-cuff systolic blood pressure was significantly elevated in RRM and RRM+Cap fats comp ared with sham-operated rats. The ratios of the medial wall area of th e thoracic aorta and heart weight to body weight were significantly el evated in RRM and RRM+Cap rats compared with sham-operated rats. North ern blot analysis indicated that the ratio of AT(1) to GAPDH mRNA in t he aorta was significantly higher in RRM (1.85+/-0.52) compared with s ham-operated (0.21+/-0.04) and RRM+Cap (0.55+/-0.20) raw, In contrast, the ratio of AT(1) to GAPDH mRNA in the heart was significantly incre ased 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. Capto pril treatment without altering blood pressure in RRM rats prevents th e increase in AT(1) mRNA in the aorta but not the heart, These results suggest that different tissue-specific mechanisms of AT(1) gene regul ation exist ie, in aorta, an Ang II- or kinin-dependent mechanism is o perant whereas in heart, RRM-induced upregulation of AT(1) mRNA may be pressure dependent.