Plasma endothelin and big endothelin levels in cardiovascular subjects and effects of bosentan

Yumi Miyauchi1,2, Seiji Maeda1, Satoshi Sakai1,2, Jun Sugawara1, Nobutake Shimojoh1,2, Subrina Jesmin1, Shigeyuki Watanabe2, Satoshi Homma2, Kazutaka Aonuma2, Takashi Miyauchi1,2. 1University of Tsukuba, Center of TARA, 305-8577, Japan, 2University of Tsukuba, Cardiovascular Division, Department of Internal Medicine, 305-8575, Japan.

Purpose Various cardiovascular diseases especially metabolic syndrome is partly prevented by exercise training. Endothelin is a strong vasoconstrictor with vasoproliferative activity. The purpose is to study whether changes in endothelin production is involved in this beneficial effects of training, and whether endothelin antagonist becomes anti-metabolic syndrome treatment. For this purpase, we also measured plasma endothelin and big endothelin levels in patients with cardiovascular diseases.

Methods and Results (1) Plasma endothelin leves increased with aging. Plasma levels of both endothelin and big endothelin were increased in hemodialysis patients, and intensity of increase was higher in endothelin than in big endothelin. Plasma endothelin and big endothelin levels were increased in patients with acute and chronic heart failure. We also measured plasma endothelin in aged healthy subjects before and after 3 months of exercise training (jogging), and plasma endothelin level decreased significantly after exercise training. We also applied high-dose bosentan (500 mg od/person po: 4-fold higher than in treatment of patients with pulmonary hypertension) to these subjects. Before training, carotid arterial compliance increased significantly with administration of high-dose bosentan, whereas after training the increase by high-dose bosentan was abolished.

Conclusion and Discussion Plasma endothelin and big endothelin levels were increased in various cardiovascular diseases especially metabolic syndrome, and the beneficial effects of exercise training on these patients were partly attributed to decrease in endothelin production. When these patients can not do exercise training, endothelin antagonist application colud partly be an alternative therapy for increasing arterial compliance (distensibility) thereby improving cardiovascular diseases.