| Preface3 - hydroxy - 3 - methylglutaryl - coenzyme A ( HMG - CoA) reducase inhibitor, called statins, has been used in the treatment of hypercholesterolemia for several decades, statins compelitively inhibit HMG - CoA reducase, the enzyme that catalyzes the rate - limiting step in chelosterol biosynthesis. The effects of statins have been mainly attributed to their cholesterol - lowering properties, but there are growing evidences that some beneficial effects of these agents may be independent of plasma cholesterol levels. These nonlipid mechanisms of ststins may contribute to the cardiovascular event reduction and ex-plain the early clinical benefit in clincal trials. Angiotensin II ( Ang II ) plays crucial role in the pathogenesis of atherosclerosis and hyper-tension, its most cardiovascular effects are mediated by the Ang II type 1 receptor ( AT1 - R) . AT1- R of VSMCs are increased in ather-osclerotic lesions and the neointima after balloon injury. Upregulation of AT1 - R and enhancement of Ang II actions in the vessel wall con-tribute to atherogenesis. To evaluate the effects of statins on expres-sion of AT1 - R in vascular wall, the present study is that spontane-ously hypertensive rats (SHR) , an animal model with profound vas-cular dysfunction on the basis of hypertension in the absence of lipid disorders, were treated with atorvastatin, to discuss the mechanism bywhich statins may exert benificial effects independent of lipid - lower-ing.Experimental MaterialsSpontaneously hypertensive rats, Atorvastatin , TRIZOL and oth-er semi - quantitative reverse transcription - polymerase chain reaction reagents, AT1 - R rabbit polyclonal anti - body, goat anti - rabbit secondary antibody, AT1 - R and GADPH sense and antisense prim-ers.Experimental MethodsTwenty male SHRs were divided into two groups: atorvastatin group and control group, treatment was continued for 4 weeks. Systolic blood pressure was measured in conscious animals with femoral intuba-tion , recorded and analyzed by BL - 140 biofunction experimental sys-tem. AT1 - R gene and protein of artery were assessed by RT - PCR and Wester blot studies: Abdominal aorta were isolated, total RNA were obtained with TRIzol reagent, changed RNA into cDNA by the process of reverse transcription, detected the expression of AT1 - R and GADPH mRNA by PCR reaction and electrophoresis; Membrane proteins of abdomial aorta were obtained and electrophoresed through polyacrylamide gel, proteins were bloted to nitrocellulose membranes, immunblotting was performed by AT1 - R rabbit polyclonal antibody and secondary antibody, electrophoretic images were analyzed by Che-mi Imager 5500. lastly, calculated the values representing the expres-sive levels of mRNA and protein.ResultsBody weight of two groups was similar after 4 weeks treatment. Systolic blood pressure was 171. 4 ?. 7mmHg in statin - treated rats, which was lower than 202. 4 ?0. 6 mmHg in control animals ( P < 0. 05) . Vascular AT1 - R mRNA concentration was 56. 29 ?. 5% in statin - treated group , which was downregulated comparing with that was 89. 61 ?. 2% in control rats ( P <0. 01 ) . This reduced expres-sion was translated to a marked decrease in AT, - R protein , that is 29.9 ?.3 in statin - treated SHR and 8 7 . 9 ?14 . 1 in control ratsDiscussionRenin - angiotensin systenn is important humoral regulation sys-term , Ang II is an important bioactive peptide of this systerm , mainly physiological functions of Ang II were mediated by AT1 - R , AT1- R belongs to the 7 - transmembrane , G protein - coupled receptor fami-ly. Many factors, such as pressure, insolin, LDL, high salt, hyper-cholesterolemia can upregulate AT1 - R. Upregulation of AT1 - R can increase vasoconstriction , aggrandize reflection to vascular active ma-terial , enhance production of ROS , VSMC proliferation and hypertro-ply, vascluar wall thickness or stenosis.Our study indicates that atorvastatin treatment decreases vascular AT1 - R mRNA expression and AT1 - R protein level that leads to re-du...
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