title: Eplerenone reduces oxidative stress and enhances eNOS in SHR: vascular functional and structural consequences.
abstract: The aim of the present study was to evaluate the effect of the aldosterone receptor antagonist eplerenone on endothelial function, oxidative stress, and structural alterations present in spontaneously hypertensive rats (SHR). To carry out the study, male SHR (18 weeks old) were treated with two doses of eplerenone (30 and 100 mg/kg/day) for 10 weeks. A group of n = 8 untreated SHR was used as a control-vehicle group, and a group of Wistar Kyoto rats (n = 8) was used as a reference of normotensive conditions. Systolic arterial pressure (SAP) was measured by the tail-cuff method. Endothelium-dependent and -independent relaxations, as well as endothelial nitric oxide synthase (eNOS) and the subunit p22phox of NAD(P)H oxidase mRNA expressions, were studied in aorta from SHR untreated or treated with eplerenone. Media/lumen ratio was also calculated in aortic preparations. In addition, levels of reduced glutathione (GSH), oxidized glutathione (GSSG), and malonyl dialdehyde (MDA) were evaluated in liver homogenates. Treatment with eplerenone reduced (p < 0.05) SAP and normalized aortic media/lumen ratio and acetylcholine relaxations. Both doses of the drug enhanced (p < 0.05) eNOS and reduced p22phox mRNA expressions. Similarly, eplerenone increased (p < 0.05) hepatic GSH/GSSG ratio, and reduced (p < 0.05) hepatic MDA levels in a comparable manner. Consequently, it could be concluded that aldosterone participates in the functional and structural vascular alterations of SHR through the diminution of nitric oxide availability and an enhancement of vascular and systemic oxidative stress.
authors.affiliation: Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Sanz-Rosa
authors.forename: M Pilar
authors.initials: MP
authors.lastname: Oubiña
authors.forename: Eva
authors.initials: E
authors.lastname: Cediel
authors.forename: Natalia
authors.initials: N
authors.lastname: De las Heras
authors.forename: Paloma
authors.initials: P
authors.lastname: Aragoncillo
authors.forename: Gloria
authors.initials: G
authors.lastname: Balfagón
authors.forename: Victoria
authors.initials: V
authors.lastname: Cachofeiro
authors.forename: Vicente
authors.initials: V
authors.lastname: Lahera
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001835:Body Weight; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D000077545:Eplerenone; D005978:Glutathione / Q000378:metabolism; D006439:Hemodynamics; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D000451:Mineralocorticoid Receptor Antagonists; D019255:NADPH Oxidases / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010750:Phosphoproteins / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013148:Spironolactone / Q000031:analogs & derivatives* / Q000494:pharmacology; D013599:Systole
chemical_list: D026901:Membrane Transport Proteins; D000451:Mineralocorticoid Receptor Antagonists; D010750:Phosphoproteins; D012333:RNA, Messenger; D013148:Spironolactone; D009569:Nitric Oxide; D000450:Aldosterone; D008315:Malondialdehyde; D000077545:Eplerenone; D052250:Nitric Oxide Synthase Type III; D019255:NADPH Oxidases; C086986:CYBA protein, human; D005978:Glutathione; D000109:Acetylcholine