Effects of Aldosterone Receptor Blockade on Collecting Duct Renin in Normotensive and Hypertensive Rats

Abstract

Collecting duct (CD) renin mRNA and protein levels are upregulated in AngII hypertensive rats by an AT1 receptor-mediated mechanism. This study was performed to determine if aldosterone (Aldo) is also involved in the regulation of CD renin. Four groups of rats: 1) Sham operated ( n=4), 2) Epleronone (specific Aldo-receptor blocker, Epl, 25 mg/day-21days; n=4), 3) AngII (minipump infusion, 60 ng/min-28days; n=4), and 4) AngII+Epl (n=4) were used. After 28 days, SBP measured by tail-cuff method was increased in AngII-infused (207±5 mmHg) and AngII+Epl (215±5 mmHg), and normal in Epl (126±5 mmHg) and Sham (136±5 mmHg) rats. Compared to Sham: 1) Total kidney AngII content increased 2-fold and 3-fold in AngII-infused and AngII+Epl-treated; but not in Epl rats. 2) Renin qRT-PCR showed that mRNA levels decreased in renal cortex of AngII-infused (0.14±0.1DU) and Epl+AngII (0.21±0.0DU) but not in Epl (0.93±0.2DU) rats. 3) In contrast, renin transcript in the medulla was suppressed in Epl (0.3±0.1DU) and augmented in the AngII-infused (1.5±0.1DU) and AngII+Epl rats (1.3±0.2DU). 4) Renin protein levels assessed by Western blot in kidney cortex decreased in all groups of rats [Epl (0.7±0.2 DU), AngII-infused (0.5±0.2DU) and AngII+Epl (0.6±0.3DU). 5) However, in the medulla renin protein levels decreased in Epl (0.6±0.2DU) but increased in AngII-infused (1.4±0.2DU) and AngII+Epl (1.6±0.3DU) rats. In conclusion, while Aldo exerts a positive influence on CD renin in normotensive rats, Aldo receptor blockade does not prevent the effect of the elevated AngII levels in the hypertensive rats. Funded by NHLBI, NCRR, AHA, LA Board of Regents.