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

1 We have previously shown that acute intravenous injections of moxonidine and clonidine increase plasma atrial natriuretic peptide (ANP), a vasodilator, diuretic and natriuretic hormone. We hypothesized that moxonidine stimulates the release of ANP, which would act on its renal receptors to cause diuresis and natriuresis, and these effects may be altered in hypertension. 2 Moxonidine (0, 10, 50, 100 or 150  μ g in 300  μ l saline) and clonidine (0, 1, 5 or 10  μ g in 300  μ l saline) injected intravenously in conscious normally hydrated normotensive Sprague–Dawley rats (SD, ∼200 g) and 12–14‐week‐old Wistar‐Kyoto (WKY) and spontaneously hypertensive rats (SHR) dose‐dependently stimulated diuresis, natriuresis, kaliuresis and cGMP excretion, with these effects being more pronounced during the first hour post‐injection. The actions of 5  μ g clonidine and 50  μ g moxonidine were inhibited by yohimbine, an α 2 ‐adrenoceptor antagonist, and efaroxan, an imidazoline I 1 ‐receptor antagonist. 3 Moxonidine (100  μ g) stimulated ( P <0.01) diuresis in SHR (0.21±0.04 vs 1.16±0.06 ml h −1 100 g −1 ), SD (0.42±0.06 vs 1.56±0.19 ml h −1 100 g −1 ) and WKY (0.12±0.04 vs 1.44±0.21 ml h −1 100 g −1 ). Moxonidine‐stimulated urine output was lower in SHR than in SD and WKY. Moxonidine‐stimulated sodium and potassium excretions were lower in SHR than in SD, but not WKY, demonstrating an influence of strain but not of pressure. Pretreatment with the natriuretic peptide antagonist anantin (5 or 10  μ g) resulted in dose‐dependent inhibition of moxonidine‐stimulated urinary actions. Anantin (10  μ g) inhibited ( P <0.01) urine output to 0.38±0.06, 0.12±0.01, and 0.16±0.04 ml h −1 100 g −1 in SD, WKY, and SHR, respectively. Moxonidine increased ( P <0.01) plasma ANP in SD (417±58 vs 1021±112 pg ml −1 ) and WKY (309±59 vs 1433±187 pg ml −1 ), and in SHR (853±96 vs 1879±229 pg ml −1 ). 4 These results demonstrate that natriuretic peptides mediate the urinary actions of moxonidine through natriuretic peptide receptors.British Journal of Pharmacology (2005) 145 , 50–56. doi: 10.1038/sj.bjp.0706146