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...

No abstract

Dystrophin-deficient myocardium is more vulnerable than normal myocardium to pressure overload in vivo. This result has two clinical implications: (1) the patients with dystrophynopathy, such as the Duchenne and the Becker types of muscular dystrophy and X-linked type of dilated cardiomyopathy, who develop arterial hypertension should be treated aggressively, and (2) they should avoid stresses that elevate blood pressure.

No abstract

Dystrophin is a cytoskeletal protein localized to the sarcolemma of skeletal and cardiac muscle, and neurons. We have recently demonstrated that a significant cardiac damage including myocytes injury, inflammation, and fibrosis, was found in dystrophin-deficient myocardium during pressure overload [Kamogawa et al., 2001: Cardiovasc Res 50:509-515]. However, little is known about how the cardiac sarcolemmal cytoskeleton produces qualitative and quantitative changes in response to pressure overload. Accordingly, we investigated dystrophin gene expression and protein accumulation during cardiac hypertrophy. Cardiac hypertrophy was produced by banding of the abdominal aorta of rats. Total RNA from the left ventricle of the heart was used for a quantitative reverse transcription-polymerase chain reaction (RT-PCR). Dystrophin mRNA expression significantly increased by 33 +/- 18% at 1 day (P < 0.05) and 45 +/- 19% at 2 days (P < 0.01) after banding, while G3PDH mRNA showed no significant change. RT-PCR for dystrophin tissue-specific exon 1 revealed that only muscle type promoter, but not non-muscle type promoter (brain and Purkinje-cell type), was activated immediately after banding. Immunohistochemistry for dystrophin showed intense cellular membrane staining with an increase in the perimeter of the myocytes by 14% at 3 days (46.3 microm, P < 0.01) and 19% at 7 days (51.2 microm, P < 0.01) after banding. Western blotting also showed dystrophin protein increased by 14 +/- 6% at 2 days (P < 0.05) and by 32 +/- 10% at 3 days (P < 0.01) after aortic banding. In conclusion, upregulation of dystrophin mRNA expression and protein accumulation occurs in response to cardiac hypertrophy. These data and the vulnerability of dystrophin-deficient myocardium to pressure overload suggest that dystrophin could play an important role in maintaining the integrity of the sarcolemma.