title: Effect of experimental hypertension on phosphoinositide hydrolysis and proto-oncogene expression in cardiovascular tissues.
abstract: Products of inositol lipid hydrolysis and levels of c-myc, c-fos and H-ras mRNAs were measured in rat left ventricle and vascular tissues 72 h and 9 days after the induction of aortic coarctation in order to examine inositol phosphate and proto-oncogene signals during the development of pressure-related cardiac and vascular structural changes. There was a significant increase in left ventricular and proximal aortic mass at both time points but no change in mesenteric resistance artery morphology in rats with coarctation. At 72 h there was a significant increase in c-myc, c-fos and H-ras mRNAs in the left ventricle of rats with coarctation, and this was accompanied by increased levels of inositol (1,4,5)-trisphosphate. Similar results were obtained in the proximal but not the distal aorta. In resistance arteries inositol phosphate production and proto-oncogene mRNA expression were unchanged. The results indicate that at 72 h aortic coarctation induced structural thickening in the left ventricle and proximal aorta and was associated with increased inositol phosphate production and stimulation of specific proto-oncogene mRNAs. By 9 days following surgery much of the structural change in these tissues was completed, and these raised cellular signals were no longer observed. The results suggest that both increased inositol lipid hydrolysis and a rise in the expression of these proto-oncogenes are important processes in the development of vascular hypertrophy seen in this model of hypertension.
authors.affiliation: Department of Medicine, Withington Hospital, Manchester, UK.
authors.forename: D H
authors.initials: DH
authors.lastname: MacIver
authors.forename: N K
authors.initials: NK
authors.lastname: Green
authors.forename: M D
authors.initials: MD
authors.lastname: Gammage
authors.forename: H
authors.initials: H
authors.lastname: Durkin
authors.forename: A S
authors.initials: AS
authors.lastname: Izzard
authors.forename: J A
authors.initials: JA
authors.lastname: Franklyn
authors.forename: A M
authors.initials: AM
authors.lastname: Heagerty
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D006352:Heart Ventricles / Q000378:metabolism*; D006973:Hypertension / Q000378:metabolism*; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000032:analysis; D007295:Inositol Phosphates / Q000378:metabolism*; D008638:Mesenteric Arteries / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D016283:Proto-Oncogene Proteins p21(ras) / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007295:Inositol Phosphates; D011518:Proto-Oncogene Proteins; D016760:Proto-Oncogene Proteins c-fos; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D015544:Inositol 1,4,5-Trisphosphate; D016283:Proto-Oncogene Proteins p21(ras)