Atrial Natriuretic Peptide Is Involved in Renal Actions of Moxonidine

Abstract

Abstract —Moxonidine, an antihypertensive imidazoline compound, reduces blood pressure by selective activation of central imidazoline I 1 -receptors and inhibition of sympathetic nerve activity and by direct actions on the kidney, with both mechanisms resulting in diuresis and natriuresis. We hypothesized that the hypotensive and renal actions of moxonidine may be mediated by atrial natriuretic peptide (ANP), a cardiac peptide involved in pressure and volume homeostasis through its vasodilatory, diuretic, and natriuretic actions. Renal parameters were measured on an hourly basis over a period of 4 hours in conscious rats that received bolus intravenous injections of moxonidine (1 to 150 μg/300 μL saline). During the first hour, moxonidine dose-dependently stimulated diuresis, natriuresis, kaliuresis, and urinary cGMP, the index of ANP activity. Moxonidine (50 μg) significantly ( P <0.001) stimulated urinary volume (0.35±0.04 versus 1.05±0.09 mL/h per 100 g), sodium (14.3±2.5 versus 51.8±6.5 μmol/h per 100 g), potassium (10.5±2.3 versus 32.3±3.2 μmol/h per 100 g), and cGMP (325±52 versus 744±120 pmol/h per 100 g). Pretreatment with a selective imidazoline receptor antagonist, efaroxan, dose-dependently inhibited moxonidine-stimulated renal parameters. Efaroxan (25 μg per rat) significantly inhibited moxonidine-stimulated diuretic and natriuretic effects and urinary cGMP excretion (744±120 versus 381±137 pmol/h per 100 g, P <0.02). The α 2 -adrenoceptor antagonist yohimbine (50 μg per rat) partially yet significantly inhibited moxonidine-stimulated diuresis and natriuresis but not cGMP excretion. Plasma ANP was dose-dependently increased by moxonidine and was inhibited by pretreatment with efaroxan (220.8±36.9 versus 100.3±31.7 pg/mL, P <0.03) but not by yohimbine. In conclusion, selective in vivo activation of imidazoline receptors by moxonidine is associated with dose-dependent diuresis, natriuresis, and kaliuresis as well as stimulated plasma ANP and urinary cGMP excretion, thus implicating ANP in the renal actions of moxonidine.