| Background and Objective Cardiac remodeling is characterized by both increase of extracellular matrix (ECM) and hypertrophic growth of the cardiocytes. The hypertrophy and fibrosis occurs in response to an increased mechanical (hemodynamic ) load on the heart in the form of pressure or volume overload ,which is characteristic of hypertension and valvular defects , or to a decrease in the functional heart tissue as seen in myocardial infarction. Cardiac hypertrophy and fibrosis is associated with an increased risk of cardiac arrhythmias, diastolic dysfunction, congestive heart failure, and death. Chronic and persistent hypertension will activate circulatory and focal rennin-angiotensin-aldosterole-system, which plays an important role in hypertension development and target organ detriments. Integrins are the important transmembrane receptor family , which link the extracellular matrix such as fibronectin and vitronectin to the hypertrophic response pathway of cardiac myocytes , plays an important role in the development of cardiac fibrosis via adhesion. RALES (randomized aldactone evaluation study) trial show that spirolactone is protective to the heart ,which catchs a new sight on the study of aldosterone and its antagonist. Based on the above possible mechanism,in this experiment ,we explore the the inhibiting effect of valsartan and spironolactone on cardiac fibrosis and the expression of integrin 1 and fibronectin in the heart of spontaneously hypertensive rats. Methods 18 6-week-old SHRs were randomly divided into 3 groups of 6 each: SHR control group , valsartan treating group(30 mg kg-1 d-1)(SHR-V) and spironolactone treating group(20 mg kg-1 d-1 )(SHR-S).6 homogenous WKY rats served as normal group(WKY).After 14 weeks, systolic blood pressure, left ventricular mass, the ratio of left ventricular mass to body weight (LVM/BW), collagen volume fraction(CVF) and perivascular collagen area(PVCA) were determined, expression of integrin 1 were studied by irnmunohistochemistry. Results Systolic blood pressure were significantly decreased in both treatment groups compared with untreated SHRs (119.17 8.01mmHg, 145.00 13.78mmHg vs 209.17 11.94mmHg ) (P<0.05) . LVM/BW[(2.80 0.12) 10-3 , (3.14 0.21) 10-3 vs(3.81 0.22) 10-3], CVF(3.21 0.22%,4.00 0.28% vs 6.45 0.4%), PVCA(0.62 0.15%, 0.94 0.56% vs 2.05 0.21%) (P<0.05) were lower in both treatment groups, the parameters in SHR-V group were even lower than in SHR-S group (P<0.05). Compared with unteated SHRs ,the expression of integrinpi was significantly reduced in SHR-V group(98.92 1.35 vs 156.87 20.33 ) (P<0.05), while the expression of fibronectin was markedly reduced in both treatment groups(200.47 16.80,213.58 8.00 vs 456.65 41.27) (P<0.05). Conclusions Long-time and persistent hypertension cause cardiac hypertrophy and fibrosis, as well as the high expression of integrinpi and fibronectin Both valsartan and spironolactone could inhibit the development of cardiac fibrosis, which involve in machenisms partly dependent on blood pressure lowering ,that is both medicine could lower blood pressure, and partly independent on blood pressure lowering, that is valsartan could also inhibt the expression of integrin β1 and fironectin,while spironolactone could inhibit the expression of fibronectin. |
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