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Abstract-Mineralocorticoid receptor blockade improves mortality early after myocardial infarction (MI). This study investigated the vascular effects of mineralocorticoid receptor blockade in the early phase postinfarction in rats. Starting immediately after coronary ligation, male Wistar rats were treated with placebo or eplerenone (100 mg/kg/d). After 7 days, hemodynamic assessment was performed and endothelial function was determined. Maximum acetylcholineinduced relaxation was significantly attenuated in aortic rings from rats with heart failure after MI, and ameliorated by eplerenone treatment. Endothelium-independent relaxation by DEA-NONOate was similar among the groups. Endothelial NO synthase phosphorylation was reduced in the aorta of MI rats and restored by eplerenone therapy. Angiotensin I-induced vasoconstriction as well as angiotensin-converting enzyme protein levels were enhanced in aortas from MI placebo rats, and reduced by mineralocorticoid receptor inhibition. Aortic reactive oxygen species formation as well as the expression of the NAD(P)H oxidase subunit p22 phox were increased after MI and normalized in eplerenone treated rats. In conclusion, mineralocorticoid receptor antagonism improved endothelial dysfunction in the early phase post-MI. Underlying mechanisms involve inhibition of vascular angiotensin-converting enzyme upregulation and improvement of endothelial NO synthase-derived NO bioavailability. Key Words: aldosterone Ⅲ acute myocardial infarction Ⅲ endothelial dysfunction Ⅲ oxidative stress C hronic heart failure is accompanied by endothelial dysfunction. 1 Increased production of vascular reactive oxygen species, especially superoxide anion (O 2 Ϫ ), as well as diminished antioxidant defense in heart failure contribute to a reduced bioavailability of NO. 2 The renin angiotensin aldosterone system (RAAS) is markedly activated and displays a central role in heart failure progression. 3,4 Aldosterone synthesis and mineralocorticoid receptors (MR) have been described in the vascular wall. 5,6 Aldosterone stimulates vascular ACE expression/activity and potentiates angiotensin II effects. 7-10 Angiotensin II and aldosterone stimulate vascular O 2 Ϫ production, promoting NO scavenging and reducing its bioavailability. [11][12][13] In healthy subjects, contradictory effects of aldosterone on endothelial function are reported. Farquharson et al 14 showed that intravenous infusion of aldosterone reduced the forearm blood flow response to acetylcholine but did not affect sodium nitroprusside-induced vasodilation, thus inducing acute endothelial dysfunction. Others reported that aldosterone increases forearm blood flow and induces vasodilatation by stimulating NO release through rapid nongenomic effects. 15 In a recent investigation, short-term and chronic aldosterone excess did not affect forearm blood flow, but enhanced the vasodilator response to exogenous NO and improved endothelium-dependent NO-mediated vasodilation in the forearm vasculature of healthy men. 16,17 However, in subjects wit...

Myocardial infarction (MI) was induced in rats by coronary ligation to compare changes in vascular reactivity from animals that developed heart failure (InfHF) with those that did not (Inf). Infarct size was similar in both groups. In vitro preparations of tail vascular bed were used to investigate the vascular responses to acetylcholine, sodium nitroprusside, and phenylephrine. Acetylcholine-induced relaxation was impaired in the Inf group (53 Ϯ 2%, n ϭ 6) when compared with Sham (80 Ϯ 2%, n ϭ 6, P Ͻ 0.05). The maximal response (E max ) to phenylephrine increased in the Inf group (423 Ϯ 10 mm Hg, n ϭ 9, P Ͻ 0.01) and decreased in InfHF (279 Ϯ 10 mm Hg, n ϭ 7, P Ͻ 0.05) when compared with Sham (319 Ϯ 11 mm Hg, n ϭ 8). Regardless of endothelial integrity, E max to phenylephrine increased in the Inf, nitro-L-arginine methyl ester, and indomethacin groups. An increased release of a prostanoid vasodilator was detected in the Inf group. Differently, the InfHF group presented a reduction of the E max to phenylephrine and an increment of nitric oxide release. This study demonstrates that MI without heart failure impairs endothelium-dependent relaxation and increases the reactivity to phenylephrine. This increase seems to involve a muscular component. The endothelium participates with an increased release of a vasodilator prostanoid, possibly to compensate the increased smooth muscle response. When heart failure follows MI, the reactivity to phenylephrine decreases, possibly due to an increased nitric oxide release.Coronary artery ligation in rats has been used as a model of chronic left ventricular failure that closely mimics human condition (Hodsman et al., 1988). Indeed, compromised cardiac function (De Felice et al., 1989;Solomon et al., 1999) and increased peripheral resistance (Drexler and Lu, 1992;Schrier and Abraham, 1999) are found in this model. Systemic vasoconstriction can result from many compensatory mechanisms, including activation of the renin-angiotensin system, activation of the sympathetic nervous system, and alterations in the synthesis of local vascular factors (Zelis and Flaim, 1982;Gschwend et al., 2003).Much has been reported regarding endothelial dysfunction in postinfarction myocardial failure (Teerlink et al., 1993(Teerlink et al., , 1994Didion et al., 1997;Bauersachs et al., 1999;Indik et al., 2001;Gschwend et al., 2003), but there is no consensus regarding vascular function in heart failure due to heterogeneity of alterations in vascular reactivity. These alterations may depend on the duration of the disease and the type of artery studied (Stassen et al., 1997a). Despite much research on vascular reactivity in postinfarction heart failure, little is known concerning vascular reactivity in a chronic phase of myocardial infarction (MI), when heart failure is absent.The purpose of this study was, in the first place, to show that there are two animal models with similar infarction areas produced by coronary ligation: chronic MI without heart failure and with heart failure and, secondly, ...

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