Molecular forms of rat angiotensinogen in plasma and brain: identification by isoelectric focusing and immunoblot analysis

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 beta-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 micromol/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 micromol/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 beta-adrenergic stimulation. In addition, angiotensinogen production by cardiac fibroblasts is under negative feedback control of angiotensin II.

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Activation of protein kinase A by atrial natriuretic peptide in neonatal rat cardiac fibroblasts: Role in regulation of the local renin-angiotensin system

Sanghi

Kumar

Smith

et al. 2005

Regulatory Peptides

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Molecular forms of rat angiotensinogen in plasma and brain: identification by isoelectric focusing and immunoblot analysis

Cited by 3 publications

References 34 publications

Novel Perspectives on Pituitary and Brain Angiotensinogen

Novel Perspectives on Pituitary and Brain Angiotensinogen

Regulation of angiotensinogen gene expression and protein in neonatal rat cardiac fibroblasts by glucocorticoid and β-adrenergic stimulation

Activation of protein kinase A by atrial natriuretic peptide in neonatal rat cardiac fibroblasts: Role in regulation of the local renin-angiotensin system

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