| Left ventricular hypertrophy (LVH), an increase in cardiac cell size without cell division, is induced by mechanical overload, neural and humoral factors such as angiotensin II(Angll), endothelin (ET)-l, a ,-adrenergic agonists and peptide growth factors. Cardiac hypertrophy has a prevalence approaching 60% in patients with hypertension, and it is the single most important contributor to cardiovascular morbidity and mortality. Antihypertensive therapy with certain drugs may prevent or reverse the cardiac hypertrophy, including angiotensin converting enzyme inhibitors (ACEI), P -adrenergic antagonists, calcium antagonists and angiotensin II receptor blockers.The molecular mechanisms including intracellular signaling pathways in cardiac hypertrophy have not been well understood. Increased intracellular calcium concentration ([Ca +]\) is known to be an important signal for cellular growth. Various experimental results demonstrated that the [Ca2+]j was higher in hypertrophic myocardial cells than in normal myocardial cells, which indicates that Ca2+ is one of the important factors in the initiation and progression of LVH. In recent years, increased sodium-hydrogen exchanger (NHE) activity related to LVH has been the subject of extensive investigation. NHE is a major regulator of pHj in the mammalian myocardium. It can also play additional roles, such as the regulation of cell volume, initiation of cell growth and proliferation, the cellular response to certain hormones and the regulation of cellular Na+ uptake. Somereports demonstrate that the NHE is activated in hypertrophic cardiac myocytes. This activation leads to a cytoplasmic alkalinization.There is a growing body of evidence that amiloride, a NHE blocker, exerts protective effects on ischemia and reperfusion injury. It also can treat arrhythmias, prevent ventricular remodeling after myocardial infarction, and reduce the hypertrophic reaction of myocardium to various factors. These data indicate that amiloride may prevent cardiac hypertrophy. Our previous investigations have reported that amiloride can prevent or reverse the cardiac hypertrophy induced by partial ligation of abdominal aorta. The present study was designed to investigate the effect of amiloride on hypertrophic myocardium, collagen content, cardiac function, intracellular [Ca2+j] and pH in adult SHR. We also wished to study further the mechanism of cardiac hypertrophy.This study was in three parts:1. The ratio of heart wet weight (HW)/body weight (BW) and the ratio of left ventricular wet weight (LVWW) / body weight (BW) of SHR were both higher than that of Sprague-Dawley (SD) rat group. In the high (7.5 mg/kg) and low (5mg/kg) dose amiloride and enalapril groups, HW/BW was decreased by 17.61%, 14.88%, 23.48% respectively, and LVWW/BW was decreased by 24.05%, 12.46%, 34.20% respectively, compared with the SHR group, and enalapril showed a more marked inhibitory effect on HW/BW and LVWW/BW than than of amiloride.In order to analyse the collagen content in myocardium, the hydroxyproline content was measured in all groups. It was 5.72 + 0.59 u g/g dry weight in the left ventricular myocardial tissue from SHR group, which was higher than that from SD group(3.73+0.78u g/g dry weight, P<0.01). The hydroxyproline content in the amiloride group was not significantly different to the SHR group (P>0.05). Bycontrast, in the enalapril group,it was 4.62 + 0.84 u g/g dry weight, which was significantly lower than SHR (P<0.05). The hydroxyproline content in the right ventricular myocardial tissue was similar in all groups. From the results above, we concluded that the collagen content in the left ventricular myocardial tissue from SHR increased markedly, which indicated that cardiac hypertrophy in SHR was characterized by left ventricular hypertrophy. Amiloride was less effective in preventing the increase in collagen content in ventricular myocardium of SHR than enalapril, which indicated that the NHE might not be responsible for the collagen accumulation of ventricular remodeling.F... |
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