Takayuki Kawamura

Effect of low-voltage electrical stimulation on angiogenic growth factors in ischaemic rat skeletal muscle.

1 Low‐voltage electrical stimulation (LVES) in skeletal muscle at a level far below the threshold of muscle contraction has been reported to promote local angiogenesis. However, the mechanism underlying the promotion of local angiogenesis by LVES has not been fully elucidated. In the present study, we evaluated whether angiogenic factors, such as vascular endotherial growth factor (VEGF), hepatocyte growth factor (HGF) and fibroblast growth factor (FGF), as well as other disadvantageous factors, such as inflammation (interleukin (IL)‐6) and hypoxia (hypoxia‐inducible factor (HIF)‐1α), contribute to the local angiogenesis produced by LVES. 2 We completely excised bilateral femoral arteries of male Sprague‐Dawley rats. After the operation, electrodes were implanted onto the centre of the fascia of the bilateral tibialis anterior (TA) muscles, tunnelled subcutaneously and exteriorized at the level of the scapulae. The right TA muscles of rats were stimulated continuously at a stimulus frequency of 50 Hz, with a 0.1 V stimulus strength and no interval, for 5 days. The left TA muscles served as controls. 3 We found that both VEGF and HGF protein were significantly increased by LVES in stimulated muscles compared with control. The VEGF level of the LVES group was 89.10 ± 17.19 ng/g, whereas that of the control group was 65.07 ± 12.88 ng/g, as determined by ELISA (P < 0.05). The HGF level of the LVES and control groups was 8.52 ± 1.96 and 5.80 ± 2.14 ng/g, respectively (P < 0.05). In contrast, there was no difference in FGF, IL‐6 and HIF‐1α between the LVES and control groups. 4 These results suggest that LVES in a hindlimb ischaemia model of rats increases not only VEGF, but also HGF, production, which may be the main mechanism responsible for the angiogenesis produced by LVES.

Effects of angiotensin-converting enzyme inhibitor and exercise training on exercise capacity and skeletal muscle.

Objective Physical fitness is closely related with cardiovascular health. We examined the effects of angiotensin-converting enzyme inhibitor, exercise training and their combination on exercise capacity as well as skeletal muscle fiber type and capillarity in spontaneously hypertensive rats (SHR). Methods Seven-week-old male SHR were allocated to four groups: sedentary control (C), treatment with perindopril (3 mg/kg per day) (Per), exercise training on a treadmill (EX), and their combination (Per + EX). Following 8-week interventions, rats were submitted to a stepwise exercise test on a treadmill. After experiments, fiber type and capillarity in soleus muscle were examined. Results Exercise capacity significantly increased in Per compared with in C. Combination of exercise training and perindopril further increased exercise capacity compared with perindopril alone, whereas there was no significant difference in exercise capacity between EX and Per + EX. Capillary density increased similarly in Per and EX compared with in C. Combination of exercise training and perindopril further increased capillary density compared with exercise training alone. The percentage of type I fiber increased only in Per + EX. Conclusions We found that in growing SHR, chronic treatment with perindopril enhances untrained exercise capacity, while it does not affect acquired exercise capacity as a result of exercise training. We also found that perindopril promotes adaptive changes of skeletal muscle in response to exercise such as increases in capillary density and percentage of type I fiber.

Chronic angiotensin-converting enzyme inhibition and Angiotensin II antagonism in rats with chronic renal failure

The current study was undertaken to compare the organ protective effects of an angiotensin-converting enzyme inhibitor, temocapril, with those of an angiotensin II type 1 receptor antagonist, CS-866 (olmesartan medoxomil), alone or combined, in the remnant kidney model of rats. Eight-week-old spontaneously hypertensive male rats were subjected to five-sixths nephrectomy. At the age of 10 weeks, the rats were randomly allocated to groups that received two doses of CS-866 (CS-L, 3 mg/kg/day; CS-H, 10 mg/kg/day), temocapril (TEM, 10 mg/kg/day), CS-866 (3 mg/kg/day) plus temocapril (10 mg/kg/day), or a vehicle alone (untreated control group). Systolic blood pressure (SBP) and urinary protein excretion (UprotV) were measured every 2 weeks. When the rats were 18 weeks old, biochemical measurement and histologic examination were performed. All the drug treatments significantly reduced SBP, UprotV, glomerular sclerosis index (GSI), relative interstitial volume (RIV), and heart weight. The hypotensive effects were on the order of combination therapy > CS-H = TEM > CS-L. Correlational analysis was based on the values for SBP and UprotV derived from the average of values obtained when the rats were 12 to 18 weeks of age. UprotV, GSI, and RIV were found to be highly correlated with SBP among the individual rats pooled from all the groups, and the correlation was maintained among the group means. A similar correlation was found between heart weight and SBP. The results suggest that the organ protective effects of temocapril, CS-866, and combination therapy are closely related to the magnitude of their antihypertensive effects.