Sauna therapy increases nitric oxide production through increasing arterial endothelial, but not inducible, nitric oxide synthase in heart failure

Abstract

Purpose: Recent studies demonstrated that vascular endothelial dysfunction is involved in pathophysiology of chronic heart failure (CHF), and is mainly due to the decreased nitric oxide (NO) production by the decreased endothelial NO synthase (eNOS) expression and the increased oxidative stress. We previously reported that sauna therapy, using far infrared-ray dry sauna at 60 degrees centigrade, improves hemodynamics, vascular endothelial and cardiac function and clinical symptoms in CHF. The purpose of this study is to investigate the mechanisms by which sauna therapy improves endothelial function. Methods: Male TO-2 cardiomyopathic hamsters were used and were treated daily by sauna in which their rectal temperature raised almost 1 degree centigrade as clinical setting. Immunohistochemistry, Western blotting, reverse transcription-polymerase chain reaction and Griess regent reaction assay were performed to assess aortic eNOS, inducible NO synthase (iNOS) and concentration of serum nitrate. Results: Both eNOS mRNA and protein expression in aortas of TO-2 decreased with age. Four-week sauna therapy significantly increased eNOS mRNA and protein expression about 2 folds compared with those without sauna, but not modulated iNOS protein expression. Serum nitrate concentrations were increased by 4-week sauna therapy compared with those without sauna. Conclusions: Repeated sauna therapy increases NO production by the upregulation of the decreased eNOS expression in cardiomyopathic hamsters with heart failure, suggesting the improvement of endothelial function in CHF.