Endogenous aldosterone contributes to acute angiotensin II-stimulated plasminogen activator inhibitor-1 and preproendothelin-1 expression in heart but not aorta.

Luther JM, Wang Z, Ma J, Makhanova N, Kim HS, Brown NJ
Endocrinology. 2009 150 (5): 2229-36

PMID: 19106220 · PMCID: PMC2671907 · DOI:10.1210/en.2008-1296

To test the hypothesis that angiotensin (Ang) II induces profibrotic gene expression through endogenous aldosterone, we measured the effect of 4 h infusion (600 ng/kg x min) of Ang II on tissue mRNA expression of plasminogen activator inhibitor 1 (PAI-1), preproendothelin-1 (ppET-1), TGF-beta, and osteopontin in wild-type (WT), aldosterone synthase-deficient (AS(-/-)), and AS(-/-) mice treated with aldosterone (either 500 ng/d for 7 d or 250 ng as a concurrent 4 h infusion). Ang II increased aldosterone in WT (P < 0.001) but not in AS(-/-) mice. Aldosterone (7 d) normalized basal aldosterone concentrations in AS(-/-) mice; however, there was no further effect of Ang II on aldosterone (P = NS). Basal cardiac and aortic PAI-1 and ppET-1 expression were similar in WT and AS(-/-) mice. Ang II-stimulated PAI-1 (P < 0.001) and ppET-1 expression (P = 0.01) was diminished in the heart of AS(-/-) mice; treatment with aldosterone for 4 h or 7 d restored PAI-1 and ppET-1 mRNA responsiveness to Ang II in the heart. Ang II increased PAI-1 (P = 0.01) expression in the aorta of AS(-/-) as well as WT mice. In the kidney, basal PAI-1, ppET-1, and TGF-beta mRNA expression was increased in AS(-/-) compared with WT mice and correlated with plasma renin activity. Ang II did not stimulate osteopontin or TGF-beta expression in the heart or kidney. Endogenous aldosterone contributes to the acute stimulatory effect of Ang II on PAI-1 and ppET-1 mRNA expression in the heart; renin activity correlates with basal profibrotic gene expression in the kidney.

MeSH Terms (17)

Aldosterone Angiotensin II Animals Aorta Blood Pressure Cytochrome P-450 CYP11B2 Drug Interactions Endothelin-1 Heart Mice Mice, Inbred C57BL Mice, Knockout Myocardium Plasminogen Activator Inhibitor 1 Receptor, Angiotensin, Type 1 Time Factors Up-Regulation

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