Urinary responses to acute moxonidine are inhibited by natriuretic peptide receptor antagonist

Rouwayda El-Ayoubi1, Ahmed Menaouar, Jolanta Gutkowska

  • 1Laboratory of Cardiovascular Biochemistry, Centre hospitalier de l'Université de Montréal-Hotel-Dieu, and Department of Medicine, Université de Montréal, Montreal (Quebec), Canada.

Insights

Moxonidine and clonidine stimulate the release of atrial natriuretic peptide (ANP), a hormone that promotes urination and sodium excretion. These effects are mediated by ANP acting on renal receptors, with some differences observed in hypertensive rats.

Area of Science:

  • Pharmacology
  • Nephrology
  • Cardiovascular Physiology

Background:

  • Previous studies indicated that moxonidine and clonidine increase plasma atrial natriuretic peptide (ANP).
  • ANP is a hormone known for its vasodilator, diuretic, and natriuretic properties.
  • Hypertension may alter the renal response to ANP-mediated effects.

Purpose of the Study:

  • To investigate if moxonidine stimulates ANP release.
  • To determine if ANP mediates diuresis and natriuresis induced by moxonidine.
  • To examine potential alterations in these effects in the context of hypertension.

Main Methods:

  • Intravenous administration of moxonidine and clonidine to normotensive (Sprague-Dawley, Wistar-Kyoto) and spontaneously hypertensive rats (SHR).
  • Dose-dependent assessment of diuresis, natriuresis, kaliuresis, and cGMP excretion.
  • Pharmacological blockade using yohimbine (alpha2-adrenoceptor antagonist) and efaroxan (imidazoline I1-receptor antagonist).
  • Administration of anantin (natriuretic peptide antagonist) to evaluate ANP's role.
  • Measurement of plasma ANP levels.

Main Results:

  • Moxonidine and clonidine dose-dependently stimulated diuresis, natriuresis, kaliuresis, and cGMP excretion, effects more pronounced in the first hour.
  • The actions of clonidine and moxonidine were inhibited by yohimbine and efaroxan.
  • Moxonidine-stimulated urine output and electrolyte excretion were lower in SHR compared to normotensive rats, suggesting strain-specific influences.
  • Anantin significantly inhibited moxonidine-induced urinary effects.
  • Moxonidine administration led to a significant increase in plasma ANP levels across all rat strains.

Conclusions:

  • Natriuretic peptides are confirmed to mediate the urinary actions of moxonidine.
  • These effects are mediated through natriuretic peptide receptors.
  • While hypertension (SHR) showed some altered responses, the primary mechanism involves ANP, indicating strain-specific, rather than pressure-specific, influences on these pathways.

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