DIFFERENTIAL GENE-EXPRESSION AND REGULATION OF ANGIOTENSIN-II RECEPTOR SUBTYPES IN RAT CARDIAC FIBROBLASTS AND CARDIOMYOCYTES IN CULTURE

Although both rat cardiac nonmyocytes (mostly fibroblasts) and cardiom yocytes have a functional angiotensin II (AngII) receptor, the regulat ion mechanism of its subtype expression in the rat heart remains unkno wn. In this study, by using a binding assay and a competitive reverse- transcriptase polymerase chain reaction, we examined the regulation of AngII types 1a and 1b (AT1a-R and AT1b-R) and type 2 receptor (AT2-R) expression in embryonal day 19 (E19) and neonatal(1-d) rat cardiac fi broblasts and cardiomyocytes. The number of AT2-R in E19 fibroblasts w as dramatically decreased (from 305 to 41 fmol/mg protein) in 1-d fibr oblasts, whereas that of AT1-R and the mRNA levels remained unchanged. The ratio of AT1a-R to AT1b-R mRNA in both E19 and 1-d fibroblasts wa s 9:1. The number of AT2-R in E19 cardiomyocytes was also significantl y decreased (from 178 to 87 fmol/mg protein) in 1-d cardiomyocytes, wh ereas the magnitude was less prominent compared with that in fibroblas ts. AT1-R expression remained unaltered in E19 and 1-d cardiomyocytes. In E19 and 1-d cardiomyocytes, the AT1b-R mRNA level was 15-fold high er than that of AT1a-R mRNA. Dexamethasone induced significant increas es in AT1a-R mRNA (2.1-fold) and numbers (1.8-fold) without changing t he affinity, whereas neither AT1b-R mRNA nor the number of AT2-R was a ffected by dexamethasone. The AT1a-R gene transcription rate, determin ed by means of a nuclear run-off assay, was increased (2-fold) by dexa methasone. The half-life of AT1a-R mRNA (18 h) was unchanged by dexame thasone. These data indicate that AngII receptor subtype expression in the rat heart is regulated in a cell- and subtype-specific manner.