Abstract
We previously demonstrated the presence of components for a renin-angiotensin system in fibroblasts cultured from neonatal rat ventricles, the regulation of expression of which has not been studied. Since glucocorticoids and β-adrenergic stimuli have been implicated in cardiac hypertrophy, and function as regulators of the circulating renin-angiotensin system, we examined the effects of dexamethasone and isoproterenol on angiotensinogen mRNA levels and protein secretion in cultured neonatal rat cardiac fibroblasts. Treatment of cardiac fibroblasts for 8 h with 10 μmol/l isoproterenol or 100 nmol/l dexamethasone increased angiotensinogen mRNA levels by 246 ± 7% and 1406 ± 207%, respectively. Over 24 h, dexamethasone and isoproterenol increased angiotensinogen secretion by 148 ± 32% and 123 ± 26%, respectively. Angiotensin II, which has been reported to be a positive regulator of angiotensinogen synthesis and secretion in liver, markedly attenuated the effects of dexamethasone and isoproterenol on angiotensinogen mRNA expression and secretion. In the presence of 1 μmol/l angiotensin II, the stimulation in angiotensinogen secretion observed with dexamethasone and isoproterenol was decreased by 62% and 76%, respectively. The negative feedback of angiotensin II on angiotensinogen expression was primarily mediated through the type one angiotensin II (AT1) receptor (IC50 = 0.30 ± 0.02 nmol/l). In summary, results from this study demonstrate that angiotensinogen mRNA levels and protein secretion in cardiac fibroblasts are positively regulated by glucocorticoid and β-adrenergic stimulation. In addition, angiotensinogen production by cardiac fibroblasts is under negative feedback control of angiotensin II.
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Received: 28 October 1999, Returned for revision: 24 November 1999, Revision received: 14 January 2000, Accepted: 26 January 2000
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Dostal, D., Booz, G. & Baker, K. Regulation of angiotensinogen gene expression and protein in neonatal rat cardiac fibroblasts by glucocorticoid and β-adrenergic stimulation. Basic Res Cardiol 95, 485–491 (2000). https://doi.org/10.1007/s003950070025
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DOI: https://doi.org/10.1007/s003950070025