The effect of non-xanthine adenosine receptor antagonist on ventricular remodeling and RAAS in chronic heart failure

Abstract

Objective To analyze the effect of non-xanthine adenosine receptor antagonist(SLV320) on the ventricular remodeling and renin-angiotensin-aldosterone system(RAAS)in animal experimental models of chronic heart failure(CHF). Methods The 40 healthy male New Zealand rabbits were received adriamycin by intravenous injection to establishing the experimental animal models and were randomly divided into 4 groups, which were high-dosage group(injected with SLV320,10.0μg·kg-1·d-1),medium-dosage group(injected with SLV320,5.0μg·kg-1·d-1),low-dosage group(injected with SLV320,2.5μg·kg-1· d-1)and furosemide group(fed with furosemide,2.0mg·kg-1·d-1).Each group had 10 rabbits and continuous treated for one week. The indexes of plasma renin activity(PRA),angiotensinⅡ(AngⅡ),aldosterone (ALD)and beta ntriuretic peptide(BNP)were detected at pre-and post-treatment,and compared among 4 groups. The indexes of left ventricular end-systolic dimension(LVESD), left ventricular end-diastolic dimension(LVEDD),left ventricular posterior wall(LVPW),left ventricle ejection fraction(LVEF),left ventricular fractional shortening(LVFS)and E/A at pre-and post-treatment were detected by echocardiography and compared among 4 groups. The wet weigh of the left and right ventricle were weigh accurately. And the indexes of left ventricle weight index(LVWI)and the body weight index(BWI)were calculated and compared among 4 groups. Results The plasma levels of PRA, Ang Ⅱ,ALD and BNP were no different among 4 groups before study(all P>0.05). The sequence of 4 groups on the plasma levels of RAASindexes was highdosage group 0.05). The sequence of 4 groups on the levels of LVEF and LVFS was high-dosage group>medium-dosage group>low-dosage group>furosemide group, and the sequences of LVESD,LVEDD,LVPW and E/A were high-dosage group<medium-dosage group<low -dosage group<furosemide group(all P<0.05). The sequences of 4 groups on the LVWI and RVWI were high-dosage group<medium-dosage group<low-dosage group<furosemide group(all P<0.05). Conclusion SLV320 can regulate the ventricular remodeling and RAAS in animal model of CHF and this effect was dose dependent. Key words: Non-xanthine adenosine receptor antagonist; Heart failure; Ventricular remodeling; Renin-angiotensin-aldosterone system