title: Changes in cardiac aldosterone and its synthase in rats with chronic heart failure: an intervention study of long-term treatment with recombinant human brain natriuretic peptide.
abstract: The physiological mechanisms involved in isoproterenol (ISO)-induced chronic heart failure (CHF) are not fully understood. In this study, we investigated local changes in cardiac aldosterone and its synthase in rats with ISO-induced CHF, and evaluated the effects of treatment with recombinant human brain natriuretic peptide (rhBNP). Sprague-Dawley rats were divided into 4 different groups. Fifty rats received subcutaneous ISO injections to induce CHF and the control group (n=10) received equal volumes of saline. After establishing the rat model, 9 CHF rats received no further treatment, rats in the low-dose group (n=8) received 22.5 μg/kg rhBNP and those in the high-dose group (n=8) received 45 μg/kg rhBNP daily for 1 month. Cardiac function was assessed by echocardiographic and hemodynamic analysis. Collagen volume fraction (CVF) was determined. Plasma and myocardial aldosterone concentrations were determined using radioimmunoassay. Myocardial aldosterone synthase (CYP11B2) was detected by quantitative real-time PCR. Cardiac function was significantly lower in the CHF group than in the control group (P<0.01), whereas CVF, plasma and myocardial aldosterone, and CYP11B2 transcription were significantly higher than in the control group (P<0.05). Low and high doses of rhBNP significantly improved hemodynamics (P<0.01) and cardiac function (P<0.05) and reduced CVF, plasma and myocardial aldosterone, and CYP11B2 transcription (P<0.05). There were no significant differences between the rhBNP dose groups (P>0.05). Elevated cardiac aldosterone and upregulation of aldosterone synthase expression were detected in rats with ISO-induced CHF. Administration of rhBNP improved hemodynamics and ventricular remodeling and reduced myocardial fibrosis, possibly by downregulating CYP11B2 transcription and reducing myocardial aldosterone synthesis.
authors.affiliation: Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
authors.forename: X Q
authors.initials: XQ
authors.lastname: Zhu
authors.affiliation: Department of Geriatrics, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
authors.forename: H S
authors.initials: HS
authors.lastname: Hong
authors.affiliation: Department of Emergency Medicine, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
authors.forename: X H
authors.initials: XH
authors.lastname: Lin
authors.affiliation: Department of Cardiology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China.
authors.forename: L L
authors.initials: LL
authors.lastname: Chen
authors.affiliation: Department of Cardiology, The Central Hospital of Enshi Autonomous Prefecture, Enshi, Hubei, China.
authors.forename: Y H
authors.initials: YH
authors.lastname: Li
mesh_terms: D000450:Aldosterone / Q000097:blood* / Q000235:genetics; D000818:Animals; D002316:Cardiotonic Agents; D002908:Chronic Disease; D003094:Collagen / Q000032:analysis; D019405:Cytochrome P-450 CYP11B2 / Q000378:metabolism*; D004195:Disease Models, Animal; D004452:Echocardiography; D005355:Fibrosis / Q000209:etiology; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol; D008134:Long-Term Care; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D045283:Natriuretic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000627:therapeutic use; D014158:Transcription, Genetic / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D002316:Cardiotonic Agents; D045283:Natriuretic Agents; D011994:Recombinant Proteins; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D003094:Collagen; D019405:Cytochrome P-450 CYP11B2; D007545:Isoproterenol