AT₂ receptor activation induces natriuresis and lowers blood pressure.

ABSTRACT:

Rationale

Compound 21 (C-21) is a highly selective nonpeptide AT2 receptor (AT2R) agonist.

Objective

To test the hypothesis that renal proximal tubule AT2Rs induce natriuresis and lower blood pressure in Sprague-Dawley rats and mice.

Methods and results

In rats, AT2R activation with intravenous C-21 increased urinary sodium excretion by 10-fold (P<0.0001); this natriuresis was abolished by direct renal interstitial infusion of specific AT2R antagonist PD-123319. C-21 increased fractional excretion of Na(+) (P<0.05) and lithium (P<0.01) without altering renal hemodynamic function. AT2R activation increased renal proximal tubule cell apical membrane AT2R protein (P<0.001) without changing total AT2R expression and internalized/inactivated Na(+)-H(+) exchanger-3 and Na(+

SUBMITTER: Kemp BA 

PROVIDER: S-EPMC4116673 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature