title: Beneficial effects of proanthocyanidins in the cardiac alterations induced by aldosterone in rat heart through mineralocorticoid receptor blockade.
abstract: Aldosterone administration in rats results in several cardiac alterations. Previous studies have demonstrated that proanthocyanidins, phenolic bioactive compounds, have cardioprotective effects. We studied the potential beneficial effects of the proanthocyanidin-rich almond skin extract (PASE) on the cardiac alterations induced by aldosterone-salt treatment, their effects in mineralocorticoid receptor activity and we sought to confirm proanthocyanidins as the specific component of the extract involved in the beneficial cardiac effects. Male Wistar rats received aldosterone (1 mg/Kg/day) +1% NaCl for 3 weeks. Half of the animals in each group were simultaneously treated with either PASE (100 mg/Kg/day) or spironolactone (200 mg/Kg/day). The ability of PASE to act as an antagonist of the mineralocorticoid receptor was examined using a transactivation assay. High performance liquid chromatography was used to identify and to isolate proanthocyanidins. Hypertension and diastolic dysfunction induced by aldosterone were abolished by treatment with PASE. Expression of the aldosterone mediator SGK-1, together with fibrotic, inflammatory and oxidative mediators were increased by aldosterone-salt treatment; these were reduced by PASE. Aldosterone-salt induced transcriptional activity of the mineralocorticoid receptor was reduced by PASE. HPLC confirmed proanthocyanidins as the compound responsible for the beneficial effects of PASE. The effects of PASE were comparable to those seen with the mineralocorticoid antagonist, spironolactone. The observed responses in the aldosterone-salt treated rats together with the antagonism of transactivation at the mineralocorticoid receptor by PASE provides evidence that the beneficial effect of this proanthocyanidin-rich almond skin extract is via as a mineralocorticoid receptor antagonist with proanthocyanidins identified as the compounds responsible for the beneficial effects of PASE.
authors.affiliation: Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain; Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Beatriz
authors.initials: B
authors.lastname: Martín-Fernández
authors.affiliation: Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: de las Heras
authors.affiliation: Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Valero-Muñoz
authors.affiliation: Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Sandra
authors.initials: S
authors.lastname: Ballesteros
authors.affiliation: Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Yi-Zhou
authors.initials: YZ
authors.lastname: Yao
authors.affiliation: Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Stanton
authors.affiliation: Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Fuller
authors.affiliation: Department of Physiology, School of Medicine, Universidad Complutense, Madrid, Spain.
authors.forename: Vicente
authors.initials: V
authors.lastname: Lahera
mesh_terms: D000450:Aldosterone / Q000633:toxicity; D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D006321:Heart / Q000187:drug effects*; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control*; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D044945:Proanthocyanidins / Q000494:pharmacology* / Q000627:therapeutic use; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D027861:Prunus / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D018161:Receptors, Mineralocorticoid / Q000235:genetics / Q000378:metabolism*; D013148:Spironolactone / Q000494:pharmacology / Q000627:therapeutic use; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000450:Aldosterone; D017874:Immediate-Early Proteins; D000451:Mineralocorticoid Receptor Antagonists; D010936:Plant Extracts; D044945:Proanthocyanidins; D017346:Protein Serine-Threonine Kinases; D018161:Receptors, Mineralocorticoid; D013148:Spironolactone; D000099184:Serum-Glucocorticoid Regulated Kinases