title: Spironolactone inhibits the activity of the Na+/H+ exchanger in the aorta of mineralocorticoid-induced hypertensive rats.
abstract: BACKGROUND
  Aldosterone can induce changes in the expression or activity of Na(+)/H(+) exchanger isoform 1 (NHE-1) in vascular smooth muscle cells. We aimed to clarify whether chronic mineralocorticoid receptor activation exerts an effect on the activity of NHE-1 in the aorta of mineralocorticoid-induced hypertensive rats.
  
  
  METHODS
  Uninephrectomized male Sprague-Dawley rats received subcutaneously 10 mg/week of desoxycorticosterone (DOCA) with or without 20 mg/kg of spironolactone, or vehicle alone (n = 20). After four weeks of treatment, the animals were sacrificed; the aorta was excised for subsequent studies, including histological analysis, RT-PCR, Western blot, measurement of NHE-1 activity and vascular contractility in the presence or absence of the selective NHE-1 inhibitor ethyl-isopropyl amiloride (EIPA).
  
  
  RESULTS
  Chronic DOCA treatment increased the NHE-1 activity, systolic and diastolic blood pressure, and aortic wall thickness. All these effects were prevented by co-treatment with Spironolactone (p < 0.05). Phenylephrine-induced vascular contractility was significantly reduced in the DOCA group when EIPA was added in the media (p < 0.05). No significant differences in NHE-1 mRNA or protein levels were detected between groups.
  
  
  CONCLUSIONS
  Chronic DOCA administration induced functional and morphological alterations in the rat aorta that are partially explained by enhanced NHE-1 activity and prevented by spironolactone. However, we did not observe changes in the NHE-1 transcript or protein levels, suggesting that the effect may be due to post-transcriptional modifications induced by mineralocorticoid receptor activation.
authors.affiliation: Laboratory of Molecular Physiology, Faculty of Medicine, Universidad de los Andes, Chile.
authors.forename: Juan E
authors.initials: JE
authors.lastname: Carreño
authors.affiliation: Laboratory of Molecular Physiology, Faculty of Medicine, Universidad de los Andes, Chile.
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Verdugo
authors.affiliation: Laboratory of Molecular Physiology, Faculty of Medicine, Universidad de los Andes, Chile.
authors.forename: Felipe
authors.initials: F
authors.lastname: Contreras
authors.affiliation: Laboratory of Molecular Physiology, Faculty of Medicine, Universidad de los Andes, Chile.
authors.forename: Felipe A
authors.initials: FA
authors.lastname: Montellano
authors.affiliation: Laboratory of Molecular Physiology, Faculty of Medicine, Universidad de los Andes, Chile.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Veloso
authors.affiliation: Department of Pathology, Yale School of Medicine, USA.
authors.forename: Kurt A
authors.initials: KA
authors.lastname: Schalper
authors.affiliation: Laboratory of Molecular Physiology, Faculty of Medicine, Universidad de los Andes, Chile.
authors.forename: Mauricio
authors.initials: M
authors.lastname: Sandoval
authors.affiliation: Laboratory of Molecular Physiology, Faculty of Medicine, Universidad de los Andes, Chile.
authors.forename: Sandra
authors.initials: S
authors.lastname: Villanueva
authors.affiliation: Laboratory of Molecular Physiology, Faculty of Medicine, Universidad de los Andes, Chile.
authors.forename: Elisa
authors.initials: E
authors.lastname: Marusic
authors.affiliation: Laboratory of Molecular Physiology, Faculty of Medicine, Universidad de los Andes, Chile cirarrazabal@uandes.cl.
authors.forename: Carlos E
authors.initials: CE
authors.lastname: Irarrazabal
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced* / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008901:Mineralocorticoids; D010656:Phenylephrine / Q000494:pharmacology; D017207:Rats, Sprague-Dawley; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013148:Spironolactone / Q000494:pharmacology*; D013194:Staining and Labeling; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D008901:Mineralocorticoids; C452850:Slc9a1 protein, rat; D000074082:Sodium-Hydrogen Exchanger 1; D017923:Sodium-Hydrogen Exchangers; D010656:Phenylephrine; D013148:Spironolactone; D003900:Desoxycorticosterone
keywords: Mineralocorticoid receptor; desoxycorticosterone; mineralocorticoid receptor antagonists; sodium-hydrogen antiporter; vasoconstriction