The Effects Of Telmisartan On The Level Of Serum Adiponectin And The Expression Of Cardiac Adiponectin Receptor 1 In Spontaneously Hypertensive Rats

IntroductionEssential Hypertension is a common cardiovascular disease. Left ventricular remodeling is target-organ damage of hypertension and an independent risk factor of heart failure, myocardial infarction, arrhythmia, sudden death and other cardiovascular events. Adiponectin (APN) is a new fat factor, which is secreted from white fat cells and can help improve insulin resistance, anti-atherosclerotic, anti-inflammatory effects.In recent years, it is found that APN is closely related to ventricular remodeling caused hypertension. Telmisartan as a competitively inhibited AngⅡreceptor 1 (AT1) antagonist, addition to lower blood pressure, can protect the heart, and reverse ventricular remodeling. Effect of telmisartan on the level of APN and APN receptor expression on cardiomyocytes may be one of the mechanisms of its cardioprotective effects.ObjectiveTo observe the level of serum adiponectin and the expression of adiponectin receptor 1 in myocardial and the impact of telmisartan on the level of serum adiponectin and the expression of adiponectin receptor 1 in myocardial in spontaneous hypertensive rat(SHR), in order to explore the role of APN in ventricular remodeling caused by hypertension and a new possible mechanism that telmisartan protects the heart against ventricular remodeling.Methods16 12-week-old spontaneously hypertensive rats (SHR) were randomly divided into SHR control group (WKY group) and SHR+telmisartan group (TEL group) and 8 12-week-old male Wistar Kyoto rats (WKY) 8 were for the Wistar control group (WKY group). The TEL group were treated by given telmisartan 5mg/kg-1.d-1 in a small amount of distilled water and the other two groups were given equal amount of distilled water by gavage. the body weight was measured per 1 week and the blood pressure was measured per 2 weeks. After 8-weeka dministration to conduct the following research:①The changes of left ventricular structure and function in rats were evaluate by echocardiograph.②To observe histological changes in myocardium and measure of myocardial collagen volume fraction (CVF) by HE staining and Masson staining.③The method of enzyme-linked immunosorbent assay (ELISA) used to detect levels of serum APN.④The AdipoRl protein expression in myocardial tissue was detected by immunohistochemical method.⑤Reverse transcription-polymerase chain reaction (RT-PCR) method was used to detect the expression of AdipoRlmRNA.Results1. The systolic blood pressure (SBP) was no difference in SHR group and TEL group before administration, but was significantly higher than WKY group. During the trial period, SBP in SHR group was gradually increased, while there was no significant change on systolic blood pressure in WKY group. Compared with SHR group, the systolic blood pressure in TEL group were significantly decreased from the first 2 weeks after administration and significantly lower than SBP in SHR control group in the same period.2. The ultrasound results showed that left ventricular posterior wall (LVPWT) and the interventricular septum (IVST) in SHR group were significantly thicker than those of WKY group, left ventricular end-diastolic diameter (LVEDD) and mitral early diastolic and late diastolic peak flow velocity ratio (E/A) were decreased compared with WKY group. Compared with SHR group, LVPWT and IVST were decreased and LVEDD and E/A value were increase in TEL group. IVST in TEL group was increased than in the WKY group, LVEDD and E/A value were decreased, but the LVPWT was no difference between the two groups. 3. Compared with the WKY group, the left ventricular mass index (LVWI) was significantly higher in SHR rats, LVWI in TEL group was lower than that in SHR group, but there was no difference when compared with the WKY.4. The size and staining of myocardial cells were normal in WKY rats and myocardial cells arranged regularly. The myocardial cell volume of SHR was increased and the nucleus has also been increased, the nuclear was deep-stained myocardial and the fibers is relatively uneven staining, myocardial cell disarray, myocardial interstitial fibroblast cell hypertrophy and hyperplasia in SHR group. The cells and nuclei slightly increased, nuclear staining slightly deeper, the arrangement of myocardial cells is relatively regular in TEL group.5. The results of myocardial tissue masson staining showed that the collagen in SHR rats myocardial tissue significantly increased and which was the fence-like arrangement around myocardial cells. The myocardial interstitial collagen also increased significantly. Compared with SHR group, myocardial cells, interstitial collagen deposition decreased significantly in TEL group. Compared with the WKY group, the CVF was significantly higher in SHR group, while the CVF was significantly lower in TEL group than that in SHR group.6. Compared with the WKY group, serum APN concentration significantly decreased in SHR group. The serum APN concentration in TEL group was significantly higher compared with SHR group, but serum APN concentration in TEL group has not yet reached the level of that in WKY group.7. The immunohistochemical staining results of myocardial tissue showed that positive staining of AdipoRl mark is brown yellow granules, widely expressed in the myocardium. More brown granules distributed in WKY group but the AdipoRl positive staining brown granules significantly reduced in SHR group. Compared with SHR group, the AdipoRl positive staining in TEL group increased. The AdipoRl expression in SHR rat heart muscle was significantly lower than that in WKY group. Compared with SHR group, the AdipoRl expression in TEL group significantly increased, but have not yet reached the level of that in WKY group.8. The results of RT-PCR showed that the expression of AdipoR1mRNA in SHR rats myocardium was significantly lower than that in WKY group. Compared with SHR group, the expression of AdipoRl mRNA significantly increased in TEL group, but have not yet reached the level of that in WKY group.Conclusions1. The blood pressure of SHR is increasing with the age and up to 20 weeks of age, it tends to be stable.2. The ventricular remodeling has occurred in 20-week-old SHR.3. The serum adiponectin levels rats is descending and the expression of cardiac adiponectin receptor 1 and its mRNA are down-regulation in o 20-week-old SHR4. Telmisartan can inhibit and reversal of the ventricular remodeling and play the role of protecting the heart in SHR,which may be by making the serum adiponectin levels increase and cardiac adiponectin receptor 1 and its mRNA up-regulation.