152S Clinical Science (2002) 103 (Suppl. 48), 152S–157S (Printed in Great Britain) Effects of aging and subsequent exercise training on gene expression of endothelin-1 in rat heart Motoyuki IEMITSU*, Takashi MIYAUCHI*, Seiji MAEDA*, Takumi TANABE‡, Yoko IRUKAYAMA-TOMOBE*, Katsutoshi GOTO , Mitsuo MATSUDA‡ and Iwao YAMAGUCHI* *Cardiovascular Division, Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan, Department of Pharmacology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan, and ‡Department of Sports Medicine, Institute of Health and Sport Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8574, Japan A B S T R A C T Endothelin-1 (ET-1) is produced by endothelial cells and cardiac myocytes. ET-1 has potent positive inotropic and chronotropic effects on heart and induces myocardial cell hypertrophy. We investigated whether gene expression of ET-1 in rat hearts is altered by aging and subsequent exercise training. We also investigated whether gene expression of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), which participate in some pathological cardiac conditions, in the rat hearts is altered by aging and subsequent exercise training. We studied mRNA expression of ET-1, ANP and BNP in hearts of sedentary young rats (Sedentary young; 4 months old), sedentary aged rats (Sedentary aged; 23 months old), and swim-trained aged rats (Trained aged; 23 months old, swimming training for 8 weeks). The left ventricle weight mass index for body weight and left ventricular end-diastolic dimension were significantly higher in the Trained aged group compared with the Sedentary aged group. These results showed that Trained aged rats developed cardiac hypertrophy with improvement of cardiac function. The mRNA expression of ET-1 in the heart was significantly higher in Sedentary aged group compared with Sedentary young group, and was significantly higher in the Trained aged group compared with the Sedentary aged group. The mRNA expression of ANP and BNP in the heart was significantly higher in Sedentary aged group compared with Sedentary young group, and was significantly higher in the Trained aged group compared with the Sedentary aged group. The present results show that mRNA expression of ET-1 in the heart is increased by aging, and that the mRNA expression is further increased by exercise-induced cardiac hypertrophy, suggesting that ET-1 in the heart may participate in these physiological cardiac adaptations. INTRODUCTION Cardiac myocytes [1] and endothelial cells [2] produce endothelin-1 (ET-1). In addition to its potent vaso- contractile effects [2], ET-1 has potent positive inotropic Key words : aged rat, ET-1, heart, swimming-training. Abbreviations : ET, endothelin ; ANP, atrial natriuretic peptide ; BNP, brain natriuretic peptide ; HR, heart rate ; RT, reverse transcription ; LVEDD, left ventricular end-diastolic dimension ; LVESD, LV end-systolic dimension ; LVW, LV weight mass ; LVW}BW, LVW index for body weight. Correspondence : Dr T. Miyauchi (e-mail t-miyauc!md.tsukuba.ac.jp). and chronotropic effects on isolated heart muscles [3,4], and induces myocardial cell hypertrophy [5]. We previously reported that the circulating plasma concen- tration of ET-1 is significantly increased by aging in humans [6], and we also reported that acute exercise # 2002 The Biochemical Society and the Medical Research Society