title: Ventricular production of natriuretic peptides and ventricular structural remodeling in hypertensive heart failure.
abstract: OBJECTIVE
  Brain natriuretic peptide (BNP) is a strong predictor of left ventricular (LV) hypertrophy (LVH) and dysfunction. However, our recent studies suggested that LVH is not necessarily associated with enhanced production of BNP in hypertension. This study aimed to clarify the relation of the characteristics of hypertrophy with the degree of gene expression of BNP in the developmental process of hypertensive heart failure.
  
  
  METHODS
  Serial changes in LV geometry, histology and atrial natriuretic peptide (ANP) and BNP mRNA levels, were assessed in a hypertensive heart failure model using Dahl salt-sensitive rats (n = 24). We further studied effects of alpha1-receptor antagonist (doxazosin: 1 mg/kg per day, n = 5) and angiotensin II type 1 receptor (AT1R) antagonist (candesartan cilexetil: 1 mg/kg per day, n = 5).
  
  
  RESULTS
  The BNP mRNA level was not elevated at the compensatory hypertrophic stage when ANP mRNA level was elevated. BNP mRNA level was increased with further progression of hypertrophy and development of fibrosis. AT1R blockade prevented such fibrosis and further progression of hypertrophy with normalization of BNP mRNA levels. Compensatory hypertrophy was not suppressed; therefore, ANP mRNA level, although decreased, was still beyond the normal level. The alpha1-receptor blockade slightly attenuated LV hypertrophy with a slight decrease in ANP mRNA levels. LV fibrosis was not prevented, and the BNP mRNA level was not decreased.
  
  
  CONCLUSIONS
  BNP gene expression is not enhanced by initial compensatory hypertrophy, but is enhanced by LV fibrosis and late stage progression of hypertrophy dependent on AT1R-mediated signaling pathway.
authors.affiliation: Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Sakata
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Masuyama
authors.forename: T
authors.initials: T
authors.lastname: Mano
authors.forename: N
authors.initials: N
authors.lastname: Nishikawa
authors.forename: T
authors.initials: T
authors.lastname: Kuzuya
authors.forename: T
authors.initials: T
authors.lastname: Miwa
authors.forename: M
authors.initials: M
authors.lastname: Hori
mesh_terms: D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics; D002303:Cardiac Output, Low / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology*; D004452:Echocardiography; D005355:Fibrosis; D006352:Heart Ventricles; D006439:Hemodynamics; D006973:Hypertension / Q000150:complications*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D045283:Natriuretic Agents / Q000096:biosynthesis*; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D020257:Ventricular Remodeling
chemical_list: D045283:Natriuretic Agents; D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor