Clodronate Liposome Ameliorated Endothelial Function And Cardiac Hypertrophy In Angiotensin ? Hypertensive Mice

Objective The present study investigated the role of macrophage in endothelial dysfunction and cardiac hypertrophy in Ang ?-inducedhypertensive mice.Methods Twenty-four C57BL/6 mice were randomly divided into four groups: normal plus PBS,normal plus Clodronate Liposome treatment(CL,0.1 ml/10 g BW,2 times/week by tail vein injection),Ang?plus PBS treatment(1.4 mg·kg-1·day-1,implanted by mini-pump),Ang ?plus CL treatment for 14 days.The systolic blood pressure(SBP)was measured by tail-cuff method,SBP was measured at 3 time points: at baseline,7days and 2 weeks after Ang ?infusion.HE staining was used to measure myocardial hypertrophy;endothelium-dependent relaxation to acetylcholine in aortic rings was determined by organ chamber bath;the protein expression of p-e Nos,p-ERK1/2(p44/p42),TNF alpha,IL-1 beta,TGF beta 1,fibronectin was determined by Western blot.Results Compared with the normal plus PBSmice,Ang ? plus PBSsignificantly increased systolic blood pressure(44%,P < 0.05),macrophage infiltration in myocardial tissue(54%,P< 0.05),heart weight(29%,P< 0.05)as well as single myocardial cell area(48%,P< 0.05),impaired acetylcholine-inducedendothelium dependent relaxation(Emax-35%,P<0.05).The treatment with CL significantly reduced SBP(-25.28%,P< 0.05),the area of single myocardial cell(-38.83%,P<0.05),and improve acetylcholine-induced endothelium dependent relaxation(Emax 12.63%,P< 0.05)in Ang ?hypertensive mice.CL treatment also restored the expression of p-e NOS,p-ERK1/2(p44/p42),TNF alpha,IL-1 beta,TGF beta 1,fibronectin induced by Ang ?(P< 0.05).Conclusion Our results demonstrate that CLprotects against Ang ?-induced endothelial dysfunction and myocardial damage and remodeling,the underlying mechanisms may involve reduction in myocardial macrophage infiltration and macrophage-derived cytokines.