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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Saadane, N. Alpert, L. Chalifour, L. E. |
| Description | Author Affiliation: Saadane N ( Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, Montréal, Québec, Canada.) |
| Abstract | Adrenoreceptor agonists induce a hypertrophic phenotype in vitro and in vivo. To investigate the molecular remodeling in chronic cardiac hypertrophy we infused adult male mice with vehicle. isoproterenol, phenylephrine or both agonists for 3, 7 or 14 days. All drugs increased cardiac mass. After minipump removal cardiac mass regressed to control levels within 7 days after PE and ISO treatment whereas ISO + PE treated hearts were incompletely regressed. ANF and beta-MHC, but not alpha-MHC, expression were increased by agonists at all time points. GATA-4, Nkx-2.5, Egr-1, c-jun and c-fos expression were increased after 3, 7 and 14 days of treatment. Expression was greatest after ISO+PE> >ISO>PE>vehicle infusion suggesting a synergistic effect of adrenoreceptor stimulation and indicating a greater effect of beta- than alpha-adrenergic action in vivo. After PE or ISO drug withdrawal the HW/BW was normal and Egr-1, c-jun, c-fos and GATA-4, but not Nkx2.5, expression dropped to control levels. HW/BW regression was incomplete after ISO+PE and elevated levels of Egr-1, c-jun and Nkx2.5 expression remained. A hydralazine-mediated reduction in blood pressure had no effect on the agonist-induced cardiac hypertrophy or gene expression. In conclusion, we found that continued agonist stimulation, and not blood pressure. is responsible for the maintained increase in gene expression. Further, we found the decrease in gene expression in the regression after drug withdrawal was gene specific. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 5 |
| Volume Number | 127 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1999-07-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Cardiomegaly Metabolism DNA-Binding Proteins Genetics Gene Expression Regulation Genes, Immediate-Early Homeodomain Proteins Receptors, Adrenergic Physiology Transcription Factors Xenopus Proteins Animals Antihypertensive Agents Pharmacology Atrial Natriuretic Factor Biosynthesis Chemically Induced GATA4 Transcription Factor Isoproterenol Mice Mice, Inbred C57BL Myosin Heavy Chains Phenylephrine Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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