Natriuretic peptide gene expression in DOCA-salt hypertension after blockade of type B endothelin receptor.
We investigated the effect of long-term in vivo blockade of the ET-1 receptor subtype B (ET(B)) with A-192621, a selective ET(B) antagonist, on atrial and ventricular natriuretic peptide (NP) gene expression in deoxycorticosterone acetate (DOCA)-salt hypertension. In this model, stimulation of the cardiac natriuretic peptide (NP) and the endothelin system and suppression of the renin-angiotensin system is observed. DOCA-salt induced significant hypertension, cardiac hypertrophy and increased NP plasma and left atrial and right and left ventricular NP gene expression. ET(B) blockade per se produced hypertension and left ventricular hypertrophy but induced little change on the levels of ventricular NP and only increased left atrial natriuretic factor (ANF) mRNA levels. Combined ET(B) blockade/DOCA-salt treatment worsened hypertension, increased left ventricular hypertrophy and induced right ventricular hypertrophy. All animals so treated had increased ventricular NP gene expression. Collagen III and beta-myosin heavy chain gene expression were enhanced in both the right and the left ventricle of DOCA-salt hypertensive rats. The results of this study suggest that the ET(B) receptor does not participate directly in the modulation of atrial or ventricular NP gene expression and that this receptor mediates a protective cardiovascular function. ET(B) blockade can induce significant ventricular hypertrophy without an increase in ANF or brain NP gene expression.
Bianciotti
Liliana G
LG
University of Ottawa Heart Institute and the Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, Ontario K1Y 4W7, Canada.
de Bold
Adolfo J
AJ
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics*; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone; D065128:Endothelin Receptor Antagonists; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D009929:Organ Size / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044023:Receptor, Endothelin B; D012982:Sodium, Dietary; D014158:Transcription, Genetic
C120508:A 192621; D065128:Endothelin Receptor Antagonists; D011759:Pyrrolidines; D044023:Receptor, Endothelin B; D012982:Sodium, Dietary; D020097:Natriuretic Peptide, Brain; D003900:Desoxycorticosterone; D009320:Atrial Natriuretic Factor