Repeated Sauna Therapy Increases Arterial Endothelial Nitric Oxide Synthase Expression and Nitric Oxide Production in Cardiomyopathic Hamsters

Abstract

n patients with chronic heart failure (CHF), vascular resistance is increased through the activation of neurohumoral systems, such as the sympathetic nervous, renin-angiotensin and endothelin systems. 1 Vascular endothelial function, which is mainly represented by endothelium-dependent vasodilatory function through the production of vasodilators derived from the endothelium such as nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factors, is impaired in CHF and affects clinical symptoms. 2-5 Impaired vascular endothelial function leads to increased vascular tone and vascular remodeling, which reduces peripheral blood flow and oxygen delivery to the skeletal muscles, followed by progressive exercise intolerance and clinical symptoms. [2][3][4][5] Therapies that improve endothelial function, such as angiotensin-converting enzyme inhibitors and regular exercise, improve the clinical symptoms and prognosis in CHF. [6][7][8][9] We reported that sauna therapy at 60°C induces vasodilation of the systemic and pulmonary arteries and veins, reduces cardiac preload and afterload and improves hemodynamics, clinical symptoms and cardiac arrythmia in patients with CHF. [10][11][12] We also clarified that the beneficial effects of sauna therapy for CHF are caused by improved vascular endothelial function and the normalizing of the neurohormonal systems. 13 Furthermore, we showed that repeated sauna therapy improved the survival of cardiomyopathic hamsters with CHF. 14 Vascular endothelial dysfunction in CHF is mainly due to decreased NO production induced by decreased levels of endothelial NO synthase (eNOS) expression and increased oxidative stress. [15][16][17] We have already reported that repeated sauna therapy increased arterial eNOS protein and mRNA expressions from the normal levels in healthy hamsters. 18 However, it is important to determine whether repeated sauna therapy could increase eNOS expression downregulated by CHF. The present study aims to investigate whether repeated sauna therapy modulates eNOS expression and NO production in CHF. Methods AnimalsWe used male TO-2 cardiomyopathic hamsters (Bio Breeders, Fitchburg, MA, USA) as a model of clinical dilated cardiomyopathy. These animals develop CHF (characterized by symptoms such as general edema and pleural effusion) at around 30 weeks of age and die within a year. 19,20 Male Syrian golden hamsters (Japan SLC, Hamamatsu, Japan) served as normal controls. All animals Background Vascular endothelial dysfunction is involved in the pathophysiology of chronic heart failure (CHF). It has been reported that sauna therapy, which allows thermal vasodilation, improves vascular endothelial dysfunction in patients with CHF. The present study investigates the mechanisms through which sauna therapy improves endothelial dysfunction induced by CHF. Methods and ResultsNormal control and male TO-2 cardiomyopathic hamsters were used. Thirty-week-old TO-2 hamsters were treated daily with an experimental far infrared-ray dry sauna system for 15 min at 39°C f...

Far-Infrared Therapy

“…In particular, FIR may improve endothelial function, which is observed not only in animal studies (11,12,14) but also in one clinical study (13). Yu et al (11) suggested that the beneficial effect of FIR therapy on skin blood flow may be related to the l-arginine/nitric oxide (NO) pathway.…”

“…In this respect, Akasaki et al (12) found that repeated FIR therapy could upregulate endothelial NO synthase (eNOS) expression and augment angiogenesis in an apolipoprotein E-deficient mouse model of unilateral hind limb ischemia. Moreover, Ikeda et al (14) reported that 4 wk of sauna therapy significantly increased the serum nitrate concentrations as well as the expression of mRNA and protein of eNOS in the aortas of TO-2 hamsters. In addition, Imamura et al (13) showed that 2 wk of repeated sauna therapy significantly improved vascular endothelial function, resulting in an increase in flow-mediated, endothelium-dependent dilation of the brachial artery from 4 to 5.8% in patients with coronary risk factors.…”

“…Animal studies also demonstrated that FIR improves skin blood flow (11,12), leading to the use of FIR in the treatment of ischemic lesions and necrosis of skin tissue as a result of trauma, diabetes, and peripheral arterial occlusive disease. In addition, some studies indicated that FIR therapy may improve endothelial function and reduce the frequency of some cardiovascular dis-eases (13)(14)(15). Because vascular access usually is located in the superficial site of the upper extremities of HD patients, FIR therapy may be considered as an alternative therapeutic modality for improving access flow and the function of the AVF.…”

Temporal Changes in Skin Temperature Caused by Wet and Dry Heat in Healthy Volunteers

“…The present study also indicated that skin temperature increased to a greater extent in females than in males following wet heat application. We consider this to reflect vasodilation of vessels due to excitation of water molecules resulting from release of preserved heat from the silicic acid gel of the hot pack and not the resonance phenomenon arising from subcutaneous fat [17][18][19] . However, multilateral measurement and analysis is needed for full understanding of this result 6) .…”

“…Wet heat application, such as repetitive saunas, can promote endothelial nitric oxide synthase (eNOS) activity and increase the levels of nitric oxide (NO). Therefore, water in an excited state can lead to strong vasodilatation 18) . Application of heat (43°C) also resulted in inhibition of apoptosis and modification of cell differentiation through the action of p38 mitogenactivated protein kinase (p38MAPK) and heat shock protein 27 (HSP27).…”