Effects of Spironolactone and Irbesartan on Myocardial Remolding and Its Mechanism in Renovascular Hypertensive Rats
|Course||Aviation, aerospace and maritime medicine|
|Keywords||Myocardial remodeling SGK1 CTGF AT1R ACE Angiotensin Ⅱ Aldosterone Spironolactone Irbesartan Renal hypertensive rats|
Objective To compare spironolactone, irbesartan alone and in combination on renal hypertensive rats (renovascular hypertensive rat RHR), the efficacy of myocardial remodeling, observe the myocardial tissue of AT1R, ACE, SGK1 and CTGF protein expression changes discussed spironolactone and irbesartan antihypertensive myocardial remodeling mechanisms. Methods two kidney one clip (2K1C) rat model of renal vascular hypertension in SD rats. Randomly divided into sham operation group (Sham), renal vascular hypertension model group (RHR group), spironolactone treatment group (Spi Group 20mg.kg-1.d-1), irbesartan treatment group (Irb group 50mg . kg-1.d-1) and the combination therapy group (Com group 20mg.kg-1.d-1 50mg.kg-1.d-1), the treatment group were given the drug, biweekly tail artery was measured systolic blood pressure. 8w after treatment by carotid artery cannulation Hemodynamic parameters; detect cardiac index, myocardial cell size, ventricular total protein content of cardiac hypertrophy indicators; determination of ventricular tissue hydroxyproline content, restrictive pepsin degradation method to evaluate myocardial collagen degree of cross-linking, saturated picric acid - Sirius red staining comparison groups myocardial collagen volume fraction and perivascular collagen in the myocardium size, a comprehensive evaluation of myocardial tissue fibrosis; radioimmunoassay determination of plasma and myocardial Ang II, aldosterone content; immunohistochemical determination of myocardial tissue type I and type III collagen, SGK1 and CTGF protein level changes; Western blot detection of myocardial in SGK1, CTGF, AT1R and ACE protein expression. Results 1.RHR group of rats blood pressure significantly increased; Irb and Com group blood pressure than RHR group decreased, but the the Spi group with RHR group was no significant difference. 2. Compared with Sham group, the RHR group, cardiac index, myocardial cell size, total protein content of the ventricular myocardial hydroxyproline content, myocardial interstitial and perivascular collagen area and collagen cross-linking degree increased significantly; each treatment group was able to reduce the indicators, the combination was significantly better than the single-use, thereby improving myocardial hypertrophy and fibrosis. 3. RHR group plasma and myocardial tissue Ang Ⅱ, aldosterone level higher than the Sham group; Spi and Com group Ang Ⅱ level was significantly decreased, while Irb group significantly increased; Irb and Com group aldosterone level decreased significantly, while Spi group significantly with the rise. 4 compared with Sham group, the the RHR group of of myocardial AT1R and ACE expression was significantly increased; Spi and Com group AT1R and ACE expression was significantly decreased, while irbesartan only lowered the expression of ACE does not affect AT1R expression. RHR myocardial tissue type I, type III collagen, SGK1 and CTGF expression was significantly higher than the Sham group, each treatment group was able to reduce the expression of these indicators, and the combination was significantly better than single. Conclusion spironolactone with irbesartan alone can relieve the RHR myocardial hypertrophy and myocardial fibrosis and improve cardiac function, the combination was significantly better than single, may adjust the the RHR loop and the myocardium of Ang Ⅱ, aldosterone levels, affecting myocardial type I, type III collagen, SGK1 and CTGF expression.