title: Mechanisms regulating adrenomedullin gene expression in the left ventricle: role of mechanical load.
abstract: 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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medicine, Biocenter Oulu, University of Oulu, P.O. Box 5000, 90014, Oulu, Finland.
authors.forename: Marja
authors.initials: M
authors.lastname: Luodonpää
authors.forename: Jaana
authors.initials: J
authors.lastname: Rysä
authors.forename: Sampsa
authors.initials: S
authors.lastname: Pikkarainen
authors.forename: Olli
authors.initials: O
authors.lastname: Tenhunen
authors.forename: Heikki
authors.initials: H
authors.lastname: Tokola
authors.forename: Jutta
authors.initials: J
authors.lastname: Puhakka
authors.forename: Minna
authors.initials: M
authors.lastname: Marttila
authors.forename: Olli
authors.initials: O
authors.lastname: Vuolteenaho
authors.forename: Heikki
authors.initials: H
authors.lastname: Ruskoaho
mesh_terms: 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
chemical_list: D010455:Peptides; D012333:RNA, Messenger; D001127:Arginine Vasopressin; D020097:Natriuretic Peptide, Brain; D053607:Adrenomedullin