Nipradilol, a new β-adrenergic blocker, reduces left ventricular remodeling following myocardial infarction in spontaneously hypertensive rats

Abstract

Left ventricular (LV) cavity dilation (remodeling) following myocardial infarction (MI) is a risk factor for morbidity and mortality. This study was undertaken to determine whether nipradilol, a new beta-adrenergic blocker with vasodilating action, reduces LV remodeling after MI produced by coronary ligation in spontaneously hypertensive rats. The effects on LV remodeling of the following drugs, which were administered orally for 4 weeks, were evaluated by assessing LV end-diastolic volume index (LVEDVI): (1) vehicle, (2) nipradilol, 10 mg/kg per day. (3) propranolol, 50 mg/kg per day, and (4) captopril, 30 mg/kg per day. Since LVEDVI depends on infarct size, the effects of the drugs on LVEDVI were compared between rats with a similar infarct size, i.e., moderate, 20%-40%; and large, 40%-60%, on the basis of the histological determination of infarct size. The nipradilol-treated and captopril-treated rats had significantly smaller LVEDVI than did the vehicle-treated rats with both moderate and large infarction (large infarct: 2.48 +/- 0.12 ml/kg for the vehicle group, 1.69 +/- 0.10 ml/kg for the nipradilol group, P < 0.01, and 1.79 +/- 0.14 ml/kg for the captopril group, P < 0.01). In contrast, LVEDVI-in the propranolol-treated rats was significantly greater than that in the vehicle-treated rats with a moderate infarct (2.09 +/- 0.09 ml/kg for the vehicle group versus 2.44 +/- 0.10 ml/kg for the propranolol group, P < 0.05). The results indicate that nipradilol and captopril reduce LV remodeling after MI, whereas propranolol promotes it.

Nipradilol Can Prevent Left Ventricular Systolic and Diastolic Dysfunction After Myocardial Infarction in Rats.

“…Ten mg·kg -1 ·day -1 of nipradilol was administered orally by gastric gavage once daily from 1 day after MI for 4 weeks (each group; n=8). 18,19 The dose of nipradilol used in the present study did not affect the mean arterial pressure in the MI. 18 The rats in the untreated group were administered vehicle (5% gum arabic solution) in the same manner.…”

“…Nipradilol (3,4-dihydro-8-(2-hydroxy-3-isopropylamino) propoxy-3-nitroxy-2H-1-benzopyran) is a non-selectiveadrenergic blocker that has a vasodilating action partly mediated by a nitrate moiety of its chemical structure. 16,17 Experimentally, nipradilol prevents the increase in heart weight, LV end-diastolic pressure (LVEDP) and LV enddiastolic volume index after MI, 18,19 but it is still unclear whether nipradilol prevents the progressive systolic and diastolic dysfunction that accompanies the change in the non-infarcted myocardial tissue during cardiac remodeling after MI. To elucidate the effects of nipradilol on cardiac remodeling in a rat model of MI, LV geometry and cardiac function were assessed by Doppler echocardiography and the cardiac gene expression of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), which are markers of the hypertrophic response of cardiomyocytes, and collagen I and III, which are markers of fibrosis, in non-infarcted areas of the left and right ventricles were investigated by northern blot analysis.…”

NO-Releasing Hybrids of Cardiovascular Drugs

“…(8)) is a non-selective adrenoceptor blocking agent with a weak β-adrenoreceptor blocking activity, and a direct vasodilating property due to a nitro group contained within its molecular structure [142]. Nipradilol has shown beneficial effects on cardiac remodelling, ischaemic heart diseases and blood pressure control [143,144], and its involvement in both intracellular calcium mobilization and the content of cGMP has been proposed to partially explain its pharmacological action [145]. In a recent study, it was hypothesised that mechanical stress-induced activation of intracellular signal transduction cascades is controlled by nipradilol in human aortic smooth muscle cells (HASMC) [146]: in endothelial cells, mechanical stresses are able to stimulate one or more phosphorylation cascades leading to an activation of mitogen-activated protein kinases (MAPKs) [147].…”