Potassium Canrenoate, an Aldosterone Receptor Antagonist, Reduces Isoprenaline-Induced Cardiac Fibrosis in the Rat

Abstract

The purpose of the present study was to determine whether the administration of an antagonist of aldosterone could prevent the fibrosis induced by an acute injection of isoprenaline. Male Wistar rats were submitted to one subcutaneous injection of isoprenaline (400 mg/kg) and were simultaneously treated with potassium canrenoate in drinking water (20 mg/kg/day) started 5 days before the injection of isoprenaline. Two months later, echocardiographic and hemodynamic measurements were performed. Then, the heart was prepared for morphometric histology and quantification of fibrosis in the left ventricle. Heart and left ventricular weights were increased significantly by isoprenaline. Potassium canrenoate attenuated this increase. The administration of isoprenaline increased significantly end diastolic diameter and end systolic volume compared with control. These changes were increased further with the addition of potassium canrenoate. In contrast, the fibrosis induced by isoprenaline was reduced significantly by potassium canrenoate at the three section levels. Potassium canrenoate attenuated the fibrosis but not the enhanced dilatation of the left ventricle induced by isoprenaline.

Cardiac hypertrophy induced by sustained β-adrenoreceptor activation: pathophysiological aspects

“…In this regard, an activation of aldosterone-rather than an AT II-dependent mechanism seems to largely account for b-AR-induced myocardial fibrosis. In support of this argument, both ISO-induced myocardial fibrosis and eccentric LV remodeling were prevented by aldosterone receptor antagonists [108,151,224], an effect consistent with elevation of plasma aldosterone concentrations and its urinary excretion following chronic b-AR activation [104,105,151,224]. Furthermore, an induction of myocardial fibrosis by chronic aldosterone administration has been shown in some studies [227].…”

“…A local myocardial rather than systemic activation of renin-angiotensin system seems to play a pivotal role in b-AR-mediated stimulation of myocardial growth [104,224,225]. Indeed, prevention of systemic activation of the renin-angiotensin system by chronic salt loading did not abolish ISO-induced cardiac hypertrophy and ACE upregulation in myocardial tissue [225].…”

“…Sustained b-AR activation in rats was accompanied by increased AT II concentrations both in plasma and LV myocardium [103,104,108,223,224], as well as by increased circulating renin and aldosterone levels [104,109,224,225] thus suggesting a concomitant activation of renin-angiotensin system both at systemic and myocardial levels. However, the temporal pattern of these changes is not the same [110].…”

Differential impacts of mineralocorticoid receptor antagonist potassium canrenoate on liver and renal changes in high fat diet-mediated early hepatocarcinogenesis model rats

“…The control group (CTL) received normal diet, and all others received HFD (D12451; Research Diets, Lane, NJ, USA) containing 0 (HFD group) or 300 ppm PC (HFD+PC group) for 9 weeks starting at 2 weeks after DEN initiation. PC at a dose of 300 ppm (correspondent to 50 mg/kg/day) was administered as previously reported (Bos et al, 2004). The fourth group was administered HFD and PC as well as 5,000 ppm AGIQ in the diet (HFD+PC+AGIQ group) (Nyska et al, 2016).…”

Effects of Adrenomedullin on Cardiac Oxidative Stress and Collagen Accumulation in Aldosterone-Dependent Malignant Hypertensive Rats

“…A growing body of evidence suggests that aldosterone plays an important role in extracellular matrix and collagen synthesis in myocardium (Young et al, 1994;Brilla, 2000;Zannad et al, 2000;Pitt et al, 2003;Bos et al, 2004). In patients with essential hypertension (Duprez et al, 1993;Soylu et al, 2004) and primary aldosteronism (Rossi et al, 1997;Nishimura et al, 1999), pathological patterns of left ventricular (LV) geometry are associated with elevated levels of plasma aldosterone.…”