I~P P HOPttYSIOLOff/ ELSEVIER Pathophysiology 3 (1996) 197-201 A single bout of exercise brings about capillary growth in skeletal muscle through basic fibroblast growth factor (bFGF) Shuji Oh-ishi a, Hitoshi Yamashita a, Takako Kizaki a, Naokazu Nagata b, Chandan K. Sen c, Osmo Hiinninen d, Tetsuya Izawa e, Tomonobu Sakurai f, Hideki Ohno a, * a Departments of Hygiene, National Defense Medical College, Tokorozawa 359, Japan b Internal Medicine III, National Defense Medical College, Tokorozawa 359, Japan c Department of Molecular and Cell Biology, University of California, Berkeley, CA 94729-3200, USA d Department of Physiology, Faculty of Medicine, University of Kuopio, FIN-70211 Kuopio, Finland ~ Department of Health and Sports Sciences, University of Electro-Communications, Chofu 182, Japan ~ Department of Exercise and Sport Science, Faculty of Science, Tokyo Metropolitan Universi~, Hachioji 192-03, Japan Received 22 March 1996; accepted 6 June 1996 Abstract The purpose of the present study was to investigate the effect of a single bout of exercise on the capillary growth in an in vitro angiogenesis model and its mechanism. The exercised rats were made to run continuously for 90 min at 20 m/min (0° incline) on a rodent treadmill just before sacrifice. First, we investigated the effect of soleus extracts on the capillary growth in an in vitro angiogenesis model based on the co-culture of rat interstitial cells (like smooth muscle cell) (RSMC) and bovine capillary endothelial cells (BCEC). The extracts of soleus muscle from acutely-exercised rats had higher angiogenic activity, compared with those from control rats. The expression of bFGF mRNA in soleus muscle from acutely-exercised rats was also significantly higher than in that from control rats. Next, we found that norepinephrine (NE) at the concentration of 10 .8 to 10-5 M enhanced the capillary growth in the angiogenesis model. Furthermore, the addition of 10 -7 M NE markedly enhanced the expression of bFGF mRNA in RSMC, but not in BCEC. The data obtained here suggest that the increased level of NE with physical exercise upregulates the expression of bFGF in satellite cells like RSMC, probably leading to the increased capillarization in skeletal muscle. Keywords: Rat; Angiogenesis; Endothelial cells; Interstitial cells; Norepinephrine 1. Introduction The functioning of skeletal muscle during exercise de- pends to a large extent on the perfusion of the muscle with blood. In physical training, the increased capillary supply to the exercising muscle appears to be reasonable to provide the muscle with enough oxygen and blood-borne energy substrates [1]. Actually, a number of investigators have observed that endurance training markedly increases the capillary density in skeletal muscle [1]. The mechanism of the increased capillarization, however, still remains unclear. On the other hand, our group has demonstrated that endurance training enhances the angiogenic activity in skeletal muscle [2]. So, we speculate that the angiogenic * Corresponding author. Tel.: + 81-429-951211 ext. 2282; fax: + 81- 429-965195. activity in skeletal muscle from acutely-exercised rat may also be higher than that from non-exercised rat. The pre- sent study was designed to elucidate the effect of a single bout of exercise on the capillary growth in an in vitro angiogenesis model and its mechanism. In the present study, we investigated the effect of norepinephrine (NE) as well as of the extract from skeletal muscle on the capillary growth, because the sympathetic nervous system is acti- vated by physical exercise and NE influences the blood supply and energy metabolism through the adrenergic re- ceptor [3]. Moreover, we directed our attention to basic fibroblast growth factor (bFGF), which is thought to be closely related to physiological and pathological angiogen- esis [4]. Quite recently, Yamashita et al. [5] have reported that NE stimulates the expression of bFGF in rat brown adipocyte. We hypothesized that such phenomena can also be extrapolated to skeletal muscle in addition to brown 0928-4680/96/$15.00 Copyright © 1996 Elsevier Science B.V. All rights reserved. PII S0928-4680(96)0002 1-1