JOURNAL ARTICLE

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
16391708
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 ng.kg-1.min-1, s.c.)+/-spironolactone or hydralazine (25 mg.kg-1.d-1). 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.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read
16391708
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"