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ABSTRACT: Objectives: This study is to evaluate the impact of spironolactone (SPL) on indexes of metabolic syndrome (MS) and to further investigate the mechanisms underlying its protective effects. Methods: A rat model of MS was established by administering a fat- and salt-enriched diet (FS diet). The occurrence of MS was examined by measurement of blood pressure (BP), aldosterone (ALD) content, blood lipid (BL), glucose and insulin levels. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Pancreatic gland tissue injury was assessed by β-cell apoptosis. Mineralocorticoid receptor (MR) activity, phosphatidylinositol 3-kinase/Akt (PI3-K/Akt), and phosphorylation of p38MAPK (P-p38MAPK) in pancreatic gland tissue were evaluated by western blot analysis. Results: SPL prevented hypertension, and dyslipidemia during MS induced by the intake of FS diet, but had no effect on K+ and Na+ disturbances. Furthermore, SPL significantly attenuated ALD and MR expression levels after FS diet. Finally, SPL inhibited phosphorylation protein kinase B (p-PKB) activation in the pancreatic gland tissue, a downstream target of PI3-K, and phosphorylation of p38MAPK pathway critical for cellular apoptosis. Conclusions: This study demonstrates that SPL exerts a protective effect on hypertension and dyslipidemia. This protective effect may depend, at least in part, on MAPK and PI3-K pathways.
Journal of endocrinological investigation 04/2013; · 1.57 Impact Factor
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Xiu-Di Pan,
Zhao-Hua Zeng, Li-Ying Liang,
Jian-Dong Luo,
Ai-Yi Xiao,
Qing Lai,
Yan-Hang Wen,
Dong-Feng Lu,
Wei Wang,
Zhao-Chu He,
Wen-Kai He
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ABSTRACT: This study is to evaluate the effects of Simvastatin on left ventricular hypertrophy and left ventricular function in patients with essential hypertension. Untreated or noncompliance with drug treatment patients with simple essential hypertension were treated with a therapy on the basis of using Telmisartan to decrease blood pressure (BP). There were 237 patients who had essential hypertension combined with left ventricular hypertrophy as diagnosed by echocardiography, taken after their BPs were decreased to meet the values of the standard normal. Among them, there were only 41 out of the original 237 patients, 17.3%, who had simple essential hypertension combined with left ventricular hypertrophy without any other co-existing disease. They were the patients selected for this study. All patients were randomly, indiscriminately divided into two groups: one was the control group (Group T), treated with the Telmisartan-based monotherapy; the other was the target group (Group TS), treated with the Telmisartan-based plus simvastatin therapy. The changes of left ventricular hypertrophy and left ventricular function were rediagnosed by echocardiography after 1 year. The results we obtained from this study were as follows: (i) The average BPs at the beginning of the study, of simple essential hypertension combined with left ventricular hypertrophy, were high levels (systolic blood pressure (SBP) 189.21 ± 19.91 mm Hg, diastolic blood pressure 101.40 ± 16.92 mm Hg). (ii) The Telmisartan-based plus simvastatin therapy was significantly effective in lowering the SBP (128.26 ± 9.33 mm Hg vs. 139.22 ± 16.34 mm Hg). (iii) After the 1-year treatment, the parameters of left ventricular hypertrophy in both groups were improved. Compared to group T, there were no differences in the characteristics of the subjects, including interventricular septum, left ventricular mass, left ventricular mass index, ejection fraction, left atrium inner diameter at baseline. The patients' interventricular septum (Group TS 10.30 ± 1.80 mm vs. Group T 10.99 ± 1.68 mm, P < .05), LVM (Group TS 177.43 ± 65.40 g vs. Group T 181.28 ± 65.09 g, P < .05), and LVMI (Group TS 100.97 ± 37.33 g/m(2) vs. Group T 106.54 ± 27.95 g/m(2), P < .05), all dropped more prominently (P < .05) in group TS; the ejection fraction rose more remarkably in group TS (Group TS: 57.50 ± 16.41% to 65.43 ± 11.60%, P < .01 while showing no change in Group T); the left ventricular hypertrophy reversed more significantly and the left ventricular systolic function improved more. (iv) The left atrium inner diameter of Group TS decreased (P < .01), the ratio of E/A, which indicates the left ventricular diastolic function, continued to drop further, showing no change to the trend of left ventricular diastolic function declination. Patients who have hypertension with left ventricular hypertrophy usually suffer other accompanying diseases at the same time. Telmisartan-based plus Simvastatin treatment can significantly reduce SBP, reverse left ventricular hypertrophy, improve the left ventricular systolic function, but it has no effect on reversing the left ventricular diastolic function. This experiment indicated that Simvastatin can reverse left ventricular hypertrophy and improve left systolic function.
Clinical and Experimental Hypertension 09/2011; 33(8):558-64. · 1.07 Impact Factor
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ABSTRACT: The aim of this study was to examine the function of perivascular adiposa tissue (PVAT) on vascular relaxation response in spontaneously hypertensive rats (SHR) and the modulatory effects of the atorvastatin therapy on the PVAT functions. We investigated the mechanisms of the perivascular adipocyte-derived relaxation factor (PVRF) by using isolated rat's aortic rings and isometric contraction measurements. We found that contraction of the thoracic aorta induced by phenylephrine was significantly attenuated in the presence of PVAT from normotensive Wistar-Kyoto rats (WKY group) or the spontaneously hypertensive rats treated with atorvastatin (SHR-A group, atorvastatin 50mg/kg/day), whereas this effect was not observed in the thoracic aortic rings from the control SHR (SHR group). Transferring the solution incubated with PVAT-intact thoracic aorta to PVAT-free thoracic aorta, it induced a remarkable relaxation response in the WKY but not in the control SHR. Tetraethylammoniumchloride (TEA) could block the above relaxation. It was also shown that the PVRF function was likely, depending on the extracellular [Ca(2+)]; the anti-contractile effect of PVAT could be reduced by the inhibitor of the adenosine triphosphate (ATP)-dependent potassium channels, glibenclamide, and could be reduced by the inhibitor of cyclooxygenase by indomethacin. We thus infer that the PVAT function was distorted in hypertension rats, and the lipid-lowering treatment with atorvastatin could restore the PVAT function. The function of the PVRF may involve the Ca(2+)-activated potassium channels, the ATP-dependent potassium channels in vascular smooth muscle cell (SMC), and the release of PVRF from PVAT may involve prostaglandins (PGs) and the calcium metabolism. These results provide an insight into the pathological mechanisms of hypertension development, and indicate that the PVAT may be a potential new target for the hypertensive therapy.
Clinical and Experimental Hypertension 06/2009; 31(4):355-63. · 1.07 Impact Factor
