Role of aldosterone in angiotensin II-induced cardiac and aortic inflammation, fibrosis, and hypertrophy

Mario Fritsch Neves, Farhad Amiri, Agostino Virdis, Quy N Diep, Ernesto L Schiffrin et al.
Canadian Journal of Physiology and Pharmacology 2005, 83 (11): 999-1006
Activation of the renin-angiotensin-aldosterone system is associated with increased extracellular matrix and inflammatory markers in the cardiovascular system. We evaluated the effects of aldosterone antagonism on cardiovascular structure, collagen deposition, and expression of inflammatory markers in 2-week angiotensin (Ang) II-infused rats (120, s.c.)+/-spironolactone or hydralazine (25 Aortic and cardiac collagen density was evaluated with Sirius red staining. NFkappaB and AP-1 were measured by a electrophoretic mobility shift assay, and ED-1 (macrophage marker) and vascular cell adhesion molecule-1 (VCAM-1) were measured by immunohistochemistry. Ang II increased blood pressure (176+/-2 mmHg vs. 115+/-1 mmHg in controls, p<0.01), which was attenuated by spironolactone (147+/-4 mmHg, p<0.01) and prevented by hydralazine (124+/-2 mmHg, p<0.01). Ang II enhanced left ventricular interstitial collagen type I/III deposition (4.1%+/-0.1% vs. 3.1%+/-0.2%, p<0.05), and this was attenuated by spironolactone but not hydralazine. Ang II-induced cardiac perivascular fibrosis was prevented by spironolactone and hydralazine. Ang II significantly increased cardiac AP-1 activity and ED-1 expression, which was prevented by spironolactone only. Ang II-enhanced NFkappaB activity, and VCAM-1 expression was reduced by spironolactone and hydralazine, whereas aortic hypertrophy was prevented by spironolactone and slightly reduced by hydralazine. In conclusion, blockade of mineralocorticoid receptors with spironolactone inhibited Ang II-induced aortic hypertrophy, cardiac transcription factor activation, upregulation of downstream inflammatory markers, and collagen deposition, thus preventing Ang II-induced cardiovascular damage.

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