OBJECTIVETo evaluate the effect and related mechanisms of aldosterone (ALD) on inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production in aortic adventitia.

METHODSAortic adventitias from SD rats were incubated for 6 hours with various protocols: buffer alone (control), ALD (10(-8) mol/L - 10(-6) mol/L), ALD + spironolactone (10(-5) mol/L, ALD + SP), ALD + RU486 (10(-5) mol/L), LPS 10 ng/ml (LPS), ALD + LPS (10 ng/ml), ALD + LPS + SP (10(-5) mol/L), and ALD + LPS + RU486. Nitrate/nitrite (NOx), an index of NO production, was measured by Greiss Reaction. iNOS activity was determined by isotope-labeled L-arginine convertion rate.

RESULTS(1) NOx production and iNOS activity were similar between ALD and control groups (P > 0.05). NOx production was significantly reduced while iNOS activity remained unchanged in the ALD (10(-6) mol/L) + SP group compared to ALD (10(-6) mol/L) group. NOx production by 10(-7) mol/L and 10(-6) mol/L ALD increased by 50.0% and 58.7% respectively (P < 0.01) and iNOS activity was also significantly increased (P < 0.01) in ALD + RU486 group than that in ALD group. (2) LPS significantly increased the NOx production and iNOS activity (P < 0.01) and these effects were not augmented by adding ALD to LPS (P > 0.05) and SP significantly blocked and RU486 significantly enhanced the effects by LSP and ALD on NOx production and iNOS activity (P < 0.05).

CONCLUSIONAldosterone has a dual effect on iNOS/NO through mineralocorticoid receptor and glucocorticoid receptor pathway.

Aldosterone ; pharmacology ; Animals ; Aorta, Thoracic ; metabolism ; Cells, Cultured ; Connective Tissue ; metabolism ; Male ; Nitric Oxide ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Rats ; Rats, Sprague-Dawley