Alamndine Attenuates Cardiac Hypertrophy And Fibrosis Associated With Hypertension

Aim:To determine whether Alamndine attenuates blood pressure and cardiac remodeling in spontaneously hypertensive rats,and the involved signaling pathways.Methods:Experiments were carried out in normotensive Wistar-Kyoto(WKY)rats and spontaneously hypertensive rats(SHR)with infusion of Alamndine or saline,and in neonatal rat cardiomyocytes.The heart was evaluated by echocardiography.Renin,Ang ?,Ang ?,and catecholamine were measured by ELISA.Heart sections were stained with Masson staining,Sirius red,hematoxylin-eosin,and wheat germ agglutinin.Collagen I,MMP2,MMP9,PKA,and Akt were evaluated by western blotting and qRT-PCR.Results:Alamndine infusion attenuated blood pressure,heart weight(HW)/body weight,HW/lung weight,HW/tibia length,ANP and BNP mRNA level in hearts,cross-sectional area of cardiomyocytes,collagen I,matrix metalloproteinase(MMP)-2,and MMP9 proteins in hearts,and cardiac fibrosis level in spontaneously hypertensive rats(SHRs)(all P<0.05).PKA levels were increased in SHR compared with WKY rats(all P<0.05).These results were confirmed in cultured neonatal rat cardiomyocytes.Alamndine improves cardiac hypertrophy by inhibiting the PKA pathway.Conclusion:Alamndine attenuates hypertension and cardiac remodeling associated with hypertension by reducing cardiac hypertrophy and fibrosis.