Coronary pressure as a determinant of B-type natriuretic peptide gene expression in isolated perfused adult rat heart.
The role of coronary flow in the regulation of ventricular B-type natriuretic peptide (BNP) gene expression was studied in isolated perfused rat heart preparation. The increase of coronary flow from 5 ml/min to 20 ml/min for 2 h resulted in a 132+/-6 mm Hg increase in aortic perfusion pressure. The changes in BNP mRNA and immunoreactive BNP (IR-BNP) levels in response to hemodynamic stress were compared to those of c-fos and adrenomedullin (ADM) gene expression. The increase of coronary flow resulted in 1.5-fold increases in the left ventricular BNP mRNA (P < 0.001) and IR-BNP (P < 0.05) levels in 2-month old rats. There was also a 1.5-fold (P < 0.05) increase in ventricular c-fos mRNA levels, whereas ADM mRNA levels decreased by 74% (P < 0.001) in the left ventricle. In 18-month old rats, the increase in coronary flow decreased left and right ventricular BNP mRNA levels by 18% (P < 0.05) and 39% (P < 0.001), respectively. There were no changes in IR-BNP peptide and c-fos mRNA levels, whereas ADM mRNA levels decreased by 46% (P < 0.001) in the left ventricles. The results show that increased aortic perfusion pressure results in differential expression of cardiac genes including up-regulation of ventricular BNP and c-fos gene expression and down-regulation of ADM gene expression. Furthermore, aging seems to elevate the threshold at which hemodynamic stress of the heart results in a response at BNP gene level.
Magga
J
J
Department of Pharmacology and Toxicology, Biocenter Oulu, University of Oulu, Finland.
Mäkinen
M
M
Romppanen
H
H
Vuolteenaho
O
O
Tokola
H
H
Marttila
M
M
Ruskoaho
H
H
D053607:Adrenomedullin; D000375:Aging / Q000502:physiology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000096:biosynthesis* / Q000235:genetics*; D002496:Central Venous Pressure / Q000502:physiology*; D003326:Coronary Circulation / Q000502:physiology; D003331:Coronary Vessels / Q000502:physiology*; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D006352:Heart Ventricles / Q000378:metabolism; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D020097:Natriuretic Peptide, Brain; D010455:Peptides / Q000378:metabolism; D010477:Perfusion; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
D010455:Peptides; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin; D012313:RNA; D009320:Atrial Natriuretic Factor