The Effect Of Fosinopril On The Level Of Serum Adiponectin And The Expression Of Adiponectin Receptor1in Spontaneously Hypertensive Rats

ObjectiveTo observe the level of serurm adiponectin and the expression of adiponectinreceptor-1in myocardial and vascular walls in spontaneous hypertensive rats(SHR) and to explore the relationship between APN、 AdipoR1and left ventricularmass index(LVWI)、 MT/LD and treatment effect of fosinpril.MethodsFourteen weeks old male SHR were randomly divided into three groups： SHRgroup， fosinopril10mg group and fosinopril20mg group；14-week old maleWistar-kyoto rats (WKY) were regarded as the control group. After8weeks, bloodpressure、 serum adiponectin、 Ang Ⅱ、 BK were detected using specificenzyme-linked immunosorbent(ELISA) assays.Radioimmunoassay was used todetermine fasting insulin(FINS);the histological changes in myocardium andvascular by HE staining； the expression of adiponectin receptor-1in myocardialtissue and vascular walls were tested by immunohistochemistrical method.Results1. There were no significant differences in FPG.Compared with WKY group，blood pressure(BP) was significantly higher in SHR group (P<0.05)； Comparedwith SHR group， blood pressure was significantly lower in Fos10mg group andFos20mg group(P<0.05)； Compared with Fos10mg group， blood pressure wassignificantly lower in Fos20mg group(P<0.05). 2. Compared with WKY group, plasma adiponectin concentration、 BK weresignificantly lower in SHR group (P<0.05), whereas FINS、 HOMA-IR、 AngⅡwere signifieantly higher in SHR group (P<0.05). Compared with SHR group,plasma adiponectin concentration、BK were significantly higher in Fos10mg groupand Fos20mg group (P<0.05)， whereas FINS、 HOMA-IR、 Ang Ⅱ weresignifieantly lower in Fos10mg group and Fos20mg group(P<0.05)； Comparedwith Fos10mg group， plasma adiponectin concentration、 BK were significantlyhigher in Fos20mg group (P<0.05)， whereas FINS、 HOMA-IR、 AngⅡ weresignifieantly lower in Fos20mg group(P<0.05).3. Compared with WKY group,HWI、 LVWI、MT、MT/LD were significantlyhigher in SHR group (P<0.05). Compared with SHR group, HWI、 LVWI、 MT、MT/LD were significantly lower in Fos10mg group and Fos20mg group (P<0.05)；Compared with Fos10mg group， HWI、 LVWI、 MT、 MT/LD were significantlylower in Fos20mg group (P<0.05).4. The size and staining of myocardial cells were normal in WKY rats andmyocardial cells arranged regularly.The myocardial cell volume of SHR wasincreased and the nucleus has also been increased,the nuclear was deep-stainedmyocardial and the fibers is relatively uneven staining,myocardial celldisarray,myocardial interstitial fibroblast cell hypertrophy and hyperplasia in SHRgroup.The cells and nuclei slightly increased,nuclear staining slightly deeper, thearrangement of myocardial cells is relatively regular in Fos10mg group.The cellsand nuclei significantly almost become normal,the arrangement of myocardialcells is almost regular in Fos20mg group.5. The shape of vascular walls were normal in WKY rats and media vascularsmooth muscle cellls arranged regularly.The tunica media accretived andmyocardial vascular smooth muscle cells disarray in SHR group.Compared with SHR group, the tunica media was thinner,the arrangement of media vascularsmooth muscle cellls were relatively regular in Fos10mg group.The cells andalmost become normal,the arrangement of the arrangement of media vascularsmooth muscle cellls were almost regular in Fos20mg group.6. The immunohistochemical staining results of myocardial tissue showed thatpositive staining of AdipoR1mark is brown yellow granules, widely expressed inthe myocardium.More brown granules distributed in WKY group but the AdipoR1positive staining brown granules significantly reduced in SHR group.Comparedwith SHR group,the AdipoR1positive staining in Fos10mg group and Fos20mggroup increased. Compared with Fos10mg group,the AdipoR1positive staining inFos20mg group increased more significantly. The AdipoR1expression in SHR ratheart muscle was significantly lower than that in WKY group.Compared with SHRgroup,the AdipoR1expression in Fos10mg group and Fos20mg group significantlyincreased.Compared with Fos10mg group,the AdipoR1expression in Fos20mggroup increased more significantly.7. The immunohistochemical staining results of vascular tissue showed thatpositive staining of AdipoR1mark is brown yellow granules, widely expressed inthe vascular.More brown granules distributed in WKY group but the AdipoR1positive staining brown granules significantly reduced in SHR group.Comparedwith SHR group, the AdipoR1positive staining in Fos10mg group and Fos20mggroup increased. Compared with Fos10mg group, the AdipoR1positive staining inFos20mg group increased more significantly. The AdipoR1expression in SHR ratvascular walls was significantly lower than that in WKY group.Compared withSHR group, the AdipoR1expression in Fos10mg group and Fos20mg groupsignificantly increased.Compared with Fos10mg group, the AdipoR1expression inFos20mg group increased more significantly. 8. In WKY group and SHR group， Stepwise multivariate logistic regressionanalysis was performed to determine the predictive variables of BP among BW,APN, FPG, FINS, HOMA-IR, AngⅡ, BK, HW, LVW, HWI, LVWI, MT, LD,MT/LD, AdipoR1, which showed that BP, APN, HOMA-IR, AngⅡ,AdipoR1werethe independent predictors.9. In WKY group and SHR group， Stepwise multivariate logistic regressionanalysis was performed to determine the predictive variables of LVWI among BW,BP, APN, HOMA-IR, AngⅡ, BK, HW, LVW, HWI, AdipoR1, which showed thatAPN, HOMA-IR, BP,AdipoR1were the independent predietors.10. In WKY group and SHR group， Stepwise multivariate logistic regressionanalysis was performed to determine the predictive variables of MT/LD amongBW, BP, APN, HOMA-IR, Ang Ⅱ, BK, MT, LD, which showed that APN,HOMA-IR, BP,AdipoR1were the independent predietors.11. Compared with the10mg group, the changes of BP、 APN、 HOMA-IR、AngⅡ、BK、HWI、LVWI、MT、MT/LD and AdipoR1were even greater value inthe20mg group.12. After8-weeks treatment with Fosinopril, Stepwise multivariate logisticregression analysis was performed to determine the predictive variables of BPamong BW, APN, FPG, FINS, HOMA-IR, AngⅡ, BK, HW, LVW, HWI, LVWI, MT,LD, MT/LD, which showed that APN, HOMA-IR,AngⅡ,BK,AdipoR1were theindependent predictors.13. After8-weeks treatment with Fosinopril, Stepwise multivariate logisticregression analysis was performed to determine the predictive variables of LVWIamong BW, BP, APN, FPG, FINS, HOMA-IR, AngⅡ, BK, HW, LVW, HWI, MT,LD, MT/LD, AdipoR1, which showed that APN, HOMA-IR,AngⅡ,BK,AdipoR1were the independent predictors. 14. After8-weeks treatment with Fosinopril, Stepwise multivariate logisticregression analysis was performed to determine the predictive variables of MT/LDamong BW, APN, FPG, FINS, HOMA-IR, AngⅡ, BK, HW, LVW, HWI, LVWI, MT,LD, AdipoR1, which showed that APN, HOMA-IR,AngⅡ,BK,AdipoR1were theindependent predictors.Conclusion1.The concentration of adiponectin、 BK were lower in SHR， the AngⅡ、HOMA-IR were higher in SHR.2.The ventricular remodeling and vascular remodeling have occurred SHR.3.The expression of cardiac and vascular adiponectin receptor1aredown-regulation in SHR.4.Fosinopril could inhibit and reversal of the ventricular remodeling andvascular remodeling, which may be by raising the level of APN, increasesadiponectin receptor1, improving insulin resistance, reducing the level of AngⅡ,raising the level of BK.