Key result
Eplerenone matches triple therapy for BP reduction but achieves greater suppression of vascular inflammation.
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OBJECTIVE: To investigate the participation of aldosterone in the vascular inflammatory process associated with hypertension, as well as the possible involvement of the NFkappaB/IkappaB system. METHODS: 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)-1beta, IL-6 and tumour necrosis factor alpha (TNFalpha) were measured. Likewise, the aortic expression of the nuclear factor kappaB (NFkappaB) p50 subunit precursor, p105, and its inhibitor (IkappaB) were measured. RESULTS: SHR showed higher aortic expression of IL-1beta, IL-6 and TNFalpha than WKY (P < 0.05) and higher plasma levels of IL-1beta and IL-6 than WKY (P < 0.05). Moreover, SHR also presented increased aortic expression of nuclear transcription factor NFkappaB p50 subunit precursor (p105), and a reduction of its inhibitor IkappaB. 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-1beta and IL-6 and aortic mRNA expression of IL-1beta, IL-6 and TNFalpha. 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 IkappaB mRNA expression in a similar manner, but only eplerenone reduced NFkappaB mRNA expression. CONCLUSIONS: 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 NFkappaB/IkappaB system.
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Sanz‐Rosa et al. (2005) studied Hypertension and vascular inflammation (spontaneously hypertensive rats). Eplerenone vs. Triple antihypertensive therapy (hydralazine 20 mg/kg/day + hydrochlorothiazide 7 mg/kg/day + reserpine 0.15 mg/kg/day), untreated SHR, or normotensive WKY was evaluated on Blood pressure, aortic mRNA expression and plasma levels of IL-1beta, IL-6, TNFalpha, and aortic NFkappaB (p105) and IkappaB expression (p=<0.05). Eplerenone and triple therapy similarly lowered blood pressure in hypertensive rats (P<0.05), but eplerenone more markedly reduced vascular inflammatory cytokines and NFkappaB mRNA expression.
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