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J Renin Angiotensin Aldosterone Syst ; 16(4): 1225-31, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25997821

RESUMO

INTRODUCTION: 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.


Assuntos
Aorta/metabolismo , Hipertensão/induzido quimicamente , Hipertensão/metabolismo , Trocadores de Sódio-Hidrogênio/antagonistas & inibidores , Espironolactona/farmacologia , Animais , Pressão Sanguínea/efeitos dos fármacos , Desoxicorticosterona/farmacologia , Hipertensão/fisiopatologia , Masculino , Mineralocorticoides , Fenilefrina/farmacologia , Ratos Sprague-Dawley , Trocador 1 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/metabolismo , Coloração e Rotulagem , Vasoconstrição/efeitos dos fármacos
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