Mechanisms regulating adrenomedullin gene expression in the left ventricle: role of mechanical load.
Adrenomedullin (AM) may function as an autocrine and/or paracrine factor in the heart, but the exact mechanisms regulating cardiac AM gene expression are unknown. The aim of the present study was to characterize the role of mechanical load in regulating gene expression of AM by using two hypertensive rat strains as experimental models. Acute pressure overload was produced by arginine(8)-vasopressin (AVP, 0.05 microg/kg/min, i.v.) infusion in conscious spontaneously hypertensive rats (SHR) and double transgenic rats (dTGR) harboring both the human renin and angiotensinogen genes and in their respective normotensive strains. A significant increase in left ventricular AM mRNA levels was seen in the left ventricles of all rat strains, the increase being augmented in hypertensive strains. Direct left ventricular wall stretch in isolated, perfused rat heart preparation also activated AM gene expression. However, stretching of cultured neonatal ventricular myocytes resulted in inhibition of AM gene expression, and stretch also blocked hypoxia-induced increase in AM gene expression. The present study shows that cardiac AM gene expression is upregulated in response to pressure overload and that this upregulation may be mediated via cell types other than cardiac myocytes.
Luodonpää
Marja
M
Department of Pharmacology and Toxicology, Faculty of Medicine, Biocenter Oulu, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.
Rysä
Jaana
J
Pikkarainen
Sampsa
S
Tenhunen
Olli
O
Tokola
Heikki
H
Puhakka
Jutta
J
Marttila
Minna
M
Vuolteenaho
Olli
O
Ruskoaho
Heikki
H
D053607:Adrenomedullin; D000818:Animals; D001127:Arginine Vasopressin / Q000494:pharmacology; D005786:Gene Expression Regulation; D006352:Heart Ventricles / Q000378:metabolism*; D006801:Humans; D006973:Hypertension / Q000235:genetics / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000502:physiology; D020097:Natriuretic Peptide, Brain / Q000235:genetics; D010455:Peptides / Q000235:genetics / Q000378:metabolism*; D011312:Pressure; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
D010455:Peptides; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin