The Effects Of 20-HETE,Metabolized By CYP4A11,on Blood Pressure And Tension Of Arteries In Mice

Cytochrome P450 4A11(Cytochrome P450 4A11, CYP4A11) mainly express in kidney of human,it can hydroxylate arachidonicacid(AA) metabolism of 20-hydroxyeicosatetraenoic acid(20-HETE). 20-HETE has complex roles in different parts and sites, involved in the development of hypertension. CYP4A11 can generate 20-HETE by the hydroxylation AA, 20-HETE effect in different sites to regulate the blood pressure, but the mechanism is not clear.To research the effectsof CYP4A11 and its metabolites 20-HETE on blood pressure of mice,we established the male C57 BL / 6J miceand male eNOS mice model of hypertensionby feeding with high salt and fat diet first,then gave the inhibitor HET0016, measured the change of blood pressureand content of 20-HETE in serum and urine,to study the relationship between 20-HETE,HET0016 and blood pressure; Then we constructed the lentivirus of Cyp4a10 overexpression, transfected into male C57 BL / 6J mice and male eNOS mice to build mice model of Cyp4a10 overexpression,tested the 20-HETE content in mice to study the effects Cyp4a10 and its metabolites 20-HETE on hypertension in mice. Last we measured the effects of 20-HETE and its inhibitor HET0016 on tension of the renal artery and aorta of mice, to study the mechanism ofthe effects of 20-HETE and HET0016 on vascular tone, and made a preliminary study of the effects on hypertension.In this study, we have constructed high blood pressure models of different types of mice by feeding with high salt and fat diet and constructing the lentivirus of Cyp4a10 overexpression transfected into male mice, then we determined the vascular tension of the renal artery and aorta of mice, studied the effects of CYP4A11 and its metabolite 20-HETE on hypertension in mice in the tissue level and the overall level, made clarifications the regulation function of clear CYP4A11 and 20-HETE on blood pressure in mice initially, and studied the mechanism of 20-HETE and its inhibitor HET0016 on vascular tone.The study has established the foundation for future research of CYP4A11 and its metabolites 20-HETE on blood pressure,can be a important method to study the roles of CYP4A11 and its metabolites 20-HETE on blood pressure.