Augmentation of moxonidine-induced increase in ANP release by atrial hypertrophy

Abstract

Imidazoline receptors are divided into I(1) and I(2) subtypes. I(1)-imidazoline receptors are distributed in the heart and are upregulated during hypertension or heart failure. The aim of this study was to define the possible role of I(1)-imidazoline receptors in the regulation of atrial natriuretic peptide (ANP) release in hypertrophied atria. Experiments were performed on isolated, perfused, hypertrophied atria from remnant-kidney hypertensive rats. The relatively selective I(1)-imidazoline receptor agonist moxonidine caused a decrease in pulse pressure. Moxonidine (3, 10, and 30 micromol/l) also caused dose-dependent increases in ANP secretion, but clonidine (an alpha(2)-adrenoceptor agonist) did not. Pretreatment with efaroxan (a selective I(1)-imidazoline receptor antagonist) or rauwolscine (a selective alpha(2)-adrenoceptor antagonist) inhibited the moxonidine-induced increases in ANP secretion and interstitial ANP concentration and decrease in pulse pressure. However, the antagonistic effect of efaroxan on moxonidine-induced ANP secretion was greater than that of rauwolscine. Neither efaroxan nor rauwolscine alone has any significant effects on ANP secretion and pulse pressure. In hypertrophied atria, the moxonidine-induced increase in ANP secretion and decrease in pulse pressure were markedly augmented compared with nonhypertrophied atria, and the relative change in ANP secretion by moxonidine was positively correlated to atrial hypertrophy. The accentuation by moxonidine of ANP secretion was attenuated by efaroxan but not by rauwolscine. These results show that moxonidine increases ANP release through (preferentially) the activation of atrial I(1)-imidazoline receptors and also via different mechanisms from clonidine, and this effect is augmented in hypertrophied atria. Therefore, we suggest that cardiac I(1)-imidazoline receptors play an important role in the regulation of blood pressure.

Sympathetic Nervous System Overactivity and Its Role in the Development of Cardiovascular Disease

“…In addition to the hypotension, rilmenidine facilitates cardiac vagal baroreflexes and inhibits cardiac sympathetic baroreflexes and diminishes the increase in renal sympathetic activity produced by environmental stress (204,205). Rilmenidine also has peripheral actions such as in the kidney promoting natriuresis (236), and moxonidine increases the levels of atrial natriuretic peptide (61). Recent trials in type 1 diabetics or subjects with metabolic syndrome have yielded positive results for the imidazoline receptor agonists (96,125,191,431).…”

Effect of moxonidine and amlodipine on serum YKL-40, plasma lipids and insulin sensitivity in insulin-resistant hypertensive patients—a randomized, crossover trial

“…3 The other likely explanation is an increase in atrial natriuretic peptide secretion, which was observed after the administration of moxonidine in several experimental studies. 28,29 Other investigators did not find a significant decrease in body weight during the treatment of hypertensive patients with obesity or obesity and metabolic syndrome with either moxonidine 19 or rilmenidine. 21 However, in both studies there was a trend toward increased body weight during amlodipine therapy and decreased body weight during imidazoline receptor agonist administration.…”

The Expression of microRNA in Adult Rat Heart with Isoproterenol-Induced Cardiac Hypertrophy

“…Previous studies have shown that ISO can trigger cardiac hypertrophy by activating atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) [8]. ANP is mainly secreted by atrial myocytes, and BNP is mainly synthesized and secreted by ventricular myocytes [9,10]. During cardiac hypertrophy, ANP and BNP are secreted in large amounts [11].…”