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Adventitia plays an important role in vascular injury diseases. Nitric oxide (NO) from inducible nitric oxide synthase (iNOS) is involved in many cardiovascular diseases. iNOS/NO pathway is activated in aorta of spontaneously hypertensive rats (SHRs). The role of aldosterone in L-arginine (L-Arg)/iNOS/NO pathway of aortic adventitia is uncertain. We investigated the effect of aldosterone antagonist spironolactone on adventitial L-Arg/iNOS/NO pathway in SHRs.Twenty male SHR (10 weeks old, 220-280 g) were randomly divided into 2 groups (10 in each): untreated or treated with the aldosterone receptor antagonist, spironolactone (20 mg/kg per day) for 6 weeks. Age-matched Wistar-Kyoto rats (WKY) were used as control. Systolic blood pressure (tail-cuff method) was measured weekly. Six weeks later, the rats were sacrificed. The whole aorta was collected and aortic adventitia was isolated. iNOS activity, [(3)H]-L-Arg transport assay of aortic adventitia were carried out by isotope-labeled L-arginine conversion rate measurement, and measurement of nitrate/nitrite (NOx), an index of NO production of aortic adventitia was assayed with the Griess reaction.iNOS activity, [(3)H]-L-Arg transport and NO production were greatly increased in aortic adventitia of SHR [(12.55 +/- 2.27) pmol x mg(-1) x min(-1), (0.88 +/- 0.19) pmol x mg(-1) x min(-1) and (2.07 +/- 0.39) micromol/L)] compare versus WKY [(5.96 +/- 1.87) pmol x mg(-1) x min(-1), (0.51 +/- 0.15) pmolxmg(-1) x min(-1) and (1.55 +/- 0.32) micromol/L, P0.01], and decreased significantly by spironolactone treatment [(8.32 +/- 1.84) pmol x mg(-1) x min(-1), (0.61 +/- 0.15) pmol x mg(-1) x min(-1) and (1.64 +/- 0.27) micromol/L, P0.01].L-Arg/iNOS/NO is activated in aortic adventitia of SHR. Spironolactone can inhibit the activation of L-Arg/iNOS/NO pathway. Aldosterone may play an important role in some cardiovascular diseases such as atherosclerosis through iNOS/NO pathway.

To evaluate the effect and related mechanisms of aldosterone (ALD) on inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) production in aortic adventitia.Aortic 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.(1) NOx production and iNOS activity were similar between ALD and control groups (P0.05). 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 (P0.01) and iNOS activity was also significantly increased (P0.01) in ALD + RU486 group than that in ALD group. (2) LPS significantly increased the NOx production and iNOS activity (P0.01) and these effects were not augmented by adding ALD to LPS (P0.05) and SP significantly blocked and RU486 significantly enhanced the effects by LSP and ALD on NOx production and iNOS activity (P0.05).Aldosterone has a dual effect on iNOS/NO through mineralocorticoid receptor and glucocorticoid receptor pathway.