| Background Ventricular remodeling is the process by which ventricular size, shape and function are regulated by mechanical, neurohormonal, and genetic factor. Remodeling may be physiological and adaptive during normal growth or pathological due to myocardial infarction (MI), cardiomyopathy, hypertension, or valvular heart disease. Post infarcted remodeling, which including infarct expansion, compensatory reactive hypertrophy of the noninfarcted zone, and subsequently global ventricular dilatation, profoundly affects prognosis for survival. An intracardiac production of aldosterone has been recently reported in rat. It brings a new step to the evolution of our ideas concerning the physiology of aldosterone. However, cardiac production of aldosterone is small compared with that of adrenal, raising the question of its function in normal conditions. Moreover, the regulation of this synthesis in pathophysiologic states, such as myocardial infarction, remains unknown. This study aimed to assess the role of the activation of aldosterone on collagen synthase after myocardial infarction, and evaluate the effect of angiotensin-converting enzyme inhibitions (ACEI), spironolactone (SPI) on RAAS and post infarcted ventricular remodeling.Methods Acute myocardial infarction was produced by ligation of the left anterior descending coronary artery in Wistar rats. 24 hours after myocardial infarction , rats were randomized to untreated infarcted group(MI) or ACEI group (Cilazapril Img.kg-1.d-1), SPI group (Spironolactone 80mg-kg-1.d-1), and ACEI+SPI (Cilazapril plus Spironolactone) treated-3-infarcted groups. Sham-operated rats served as controls (Sham). After treated for two weeks, these rats were sacrificed. The weight of rats body and heart were measured. The activities of plasma AngII and aldosterone were examined by the method of radioimmunoassay test. The gene expression of cardial aldosterone synthase, collagen type I and III, angiotensinll type 1 receptor (ATwere measured by reverse transcription-polymerase chain reaction(RT-PCR) method.Results (1) There was no significant difference in the body weight among the five groups. (2) Heart weight, as well as the ratio of heart weight to body weight in the MI group were significantly increased compared with sham-operated rats, and reduced by Cilazapril, Spironolactone or combination of them to the normal, but for the ratio of heart weight to body weight in the ACEI group not to the normal. (3)MI enhanced plasma Ang II compared with sham-operated group. Treatment with Cilazapril, Spironolactone or combination of them prevented the Mi-induced rise in plasma AngII but not to the normal. (4) Plasma aldosterone was improved significantly in the MI group compared with sham-operated, and reduced by Cilazapril or combination of Spironolactone but not to the normal. Conversly, plasma aldosterone in SPI group was much higher than that in the other groups. (5) In the infarcted and noninfarcted area of left ventricle , MI induced an increase in aldosterone synthase mRNA level, which was prevented by Cilazapril or combination of Spironolactone but without reaching statistical significance. Treatment with spironolactne alone didn't change the CYP11B2 mRNA level. (6) MI elevated the gene expression of collagen type I and III in the noninfarcted and infarcted zone of the left ventricle.All treatment prevented the regulation of-4-cardiac collagen gene expression. The level of collagen type HI mRNA was lower in the SPI and ACEI+SPI group than that in the ACEI group in the infracted area. (7) MI enhanced the gene expression of AT; receptor in the infracted and noninfarcted area of the left ventricle ,which prevented by all the treatment .Conclusions (1)Postinfarcted ventricular remodeling do evidence after 2 weeks of MI , as demonstrated by the improvement of gene expression of cardiac collagen type I and HI. (2)MI is associated with an increase in plasma Angll, aldosterone and myocardial aldosterone production, which may be involved in postinfarcted ventricular remodeling, and per...
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