Participation of aldosterone in the vascular inflammatory response of spontaneously hypertensive rats: role of the NFκB/IκB system

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Abstract
To investigate the participation of aldosterone in the vascular inflammatory process associated with hypertension, as well as the possible involvement of the NFκB/IκB system. Male spontaneously hypertensive rats (SHR; 20–22 weeks old) untreated or treated with either the aldosterone receptor antagonist, eplerenone (100 mg/kg per day) or triple antihypertensive therapy (HHR: hydralazine + hydrochlorothiazide + reserpine; 20 + 7 + 0.15 mg/kg per day) were used in the study. Wistar–Kyoto rats (WKY) were used as a normotensive reference group. Aortic mRNA expression and plasma levels of interleukin (IL)-1β, IL-6 and tumour necrosis factor α (TNFα) were measured. Likewise, the aortic expression of the nuclear factor κB (NFκB) p50 subunit precursor, p105, and its inhibitor (IκB) were measured. SHR showed higher aortic expression of IL-1β, IL-6 and TNFα than WKY (P < 0.05) and higher plasma levels of IL-1β and IL-6 than WKY (P < 0.05). Moreover, SHR also presented increased aortic expression of nuclear transcription factor NFκB p50 subunit precursor (p105), and a reduction of its inhibitor IκB. Both eplerenone and HHR decreased blood pressure to a comparable extent (P < 0.05). This effect was accompanied by a reduction in plasma levels of IL-1β and IL-6 and aortic mRNA expression of IL-1β, IL-6 and TNFα. However, the effect of eplerenone was more marked, since eplerenone-treated rats showed significantly lower inflammatory parameters than SHR receiving HHR. In addition, both antihypertensive treatments increased IκB mRNA expression in a similar manner, but only eplerenone reduced NFκB mRNA expression. Aldosterone, as well as an increase in haemodynamic forces produced by hypertension, participate in the vascular inflammatory process associated with hypertension in SHR. This effect seems to be mediated by enhanced vascular expression of cytokines through a modification of the NFκB/IκB system.

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