(Hypertension. 2000;35:1215.)
© 2000 American Heart Association, Inc.
Scientific Contributions |
Atrial Natriuretic Peptide Is Involved in Renal Actions of Moxonidine
From the Laboratory of Cardiovascular Biochemistry, Centre Hospitalier de L’Universite de Montreal Research Center, Campus Hotel-Dieu, Montreal, Quebec, Canada.
Correspondence to Suhayla Mukaddam-Daher, PhD, Laboratory of Cardiovascular Biochemistry, CHUM Research Center, Campus Hotel-Dieu, Pavilion de Bullion (6-816), 3840 St-Urbain St, Montreal, Quebec, Canada, H2W 1T8. E-mail suhayla.mukaddam-daher{at}umontreal.ca
Abstract—Moxonidine, an
antihypertensive imidazoline compound, reduces blood pressure by
selective activation of central imidazoline I1-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 
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.
Key Words: atrial natriuretic factor • receptors, imidazoline • receptors, adrenergic, alpha • natriuresis • cyclic GMP • moxonidine
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