Enhancement of angiotensinogen expression in angiotensin II-dependent hypertension.

Chronic infusion of angiotensin (Ang) II leads to the development of hypertension and enhances intrarenal Ang II content to levels greater than can be explained from the circulating concentrations of the peptide. We previously reported that renal angiotensinogen (Ao) mRNA is enhanced in Ang II-dependent hypertension and may contribute to augmented intrarenal Ang II levels, but the Ao protein levels were not significantly increased. Because a high-salt diet (H/S) has been shown to suppress renal expression of Ao mRNA, we examined the effects of chronic Ang II infusion on kidney and liver Ao mRNA and protein levels in male Sprague-Dawley rats (n=12) maintained on an 8% salt diet. Ang II was administered via osmotic minipumps (40 ng/min) to 1 group (n=6) while the remaining rats were sham-operated. A H/S diet alone did not alter systolic blood pressure in sham animals (109+/-6 mm Hg at day 12); however, Ang II infusions to the H/S rats significantly increased systolic blood pressure (167+/-7 at day 12) and intrarenal Ang II content (459+/-107 fmol/g versus 270+/-42) despite a marked suppression of plasma renin activity (0.9+/-0.2 ng Ang I. mL(-1). h(-1) versus 2.8+/-1.3). Ang II infusions significantly increased kidney Ao mRNA compared with the H/S diet alone by 1.9+/-0.1-fold. Western blot analysis of kidney protein extracts showed that the Ang II-infused rats had increased kidney Ao protein levels compared with the H/S diet alone (1.9+/-0.1-fold). Liver Ao mRNA and protein and plasma Ao protein were also significantly increased by Ang II infusions. These data demonstrate the effects of Ang II infusion to stimulate Ao mRNA and protein. Thus, the augmented intrarenal Ang II in Ang II-dependent hypertension may result, in part, by a positive amplification mechanism to activate renal expression of AO: