Effect of captopril on skeletal muscle angiogenic growth factor responses to exercise.
ABSTRACT Acute exercise increases vascular endothelial growth factor (VEGF), transforming growth factor-beta(1) (TGF-beta(1)), and basic fibroblast growth factor (bFGF) mRNA levels in skeletal muscle, with the greatest increase in VEGF mRNA. VEGF functions via binding to the VEGF receptors Flk-1 and Flt-1. Captopril, an angiotensin-converting enzyme inhibitor, has been suggested to reduce the microvasculature in resting and exercising skeletal muscle. However, the molecular mechanisms responsible for this reduction have not been investigated. We hypothesized that this might occur via reduced VEGF, TGF-beta(1), bFGF, Flk-1, and Flt-1 gene expression at rest and after exercise. To investigate this, 10-wk-old female Wistar rats were placed into four groups (n = 6 each): 1) saline + rest; 2) saline + exercise; 3) 100 mg/kg ip captopril + rest; and 4) 100 mg/kg ip captopril + exercise. Exercise consisted of 1 h of running at 20 m/min on a 10 degrees incline. VEGF, TGF-beta(1), bFGF, Flk-1, and Flt-1 mRNA were analyzed from the left gastrocnemius by quantitative Northern blot. Exercise increased VEGF mRNA 4.8-fold, TGF-beta(1) mRNA 1.6-fold, and Flt-1 mRNA 1.7-fold but did not alter bFGF or Flk-1 mRNA measured 1 h after exercise. Captopril did not affect the rest or exercise levels of VEGF, TGF-beta(1), bFGF, and Flt-1 mRNA. Captopril did reduce Flk-1 mRNA 30-40%, independently of exercise. This is partially consistent with the suggestion that captopril may inhibit capillary growth.
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ABSTRACT: Objectives – There are now experimental evidences about the growth of capillary bed in response to increased functional load in skeletal muscle such as physical exercise. The objective of this review is to discuss the present state of our knowledge on the adaptive responses of the capillary bed to physical training.Topics – The skeletal muscle is known to respond to physical training and the adaptive response of the microcirculation in mammals is the high capillarity observed in trained skeletal muscles. The increase in the capillary bed after endurance training results mainly from angiogenesis, and only for a short part from changes in the capillary tortuosity. Capillary growth involves several molecular factors ; some are expressed and induced by alterations in local oxygen pressure. The specific role played by mechanical factors and shear stress for capillary growth stimulation remains the matter of debate.Future prospects – A better knowledge of molecular mechanisms involved in capillary growth is an important stage to examine the general responses to physical training. Researches on exercise-induced capillary growth have many important practical consequences, especially on therapeutic domain.Science & Sports 02/2003; 18(1):1-10. DOI:10.1016/S0765-1597(02)00052-7 · 0.54 Impact Factor
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ABSTRACT: Angiogenesis occurs in skeletal muscle in response to exercise training. To gain insight into the regulation of this process, we evaluated the mRNA expression of factors implicated in angiogenesis over the course of a training program. We studied sedentary control (n = 17) rats and both sedentary (n = 18) and exercise-trained (n = 48) rats with bilateral femoral artery ligation. Training consisted of treadmill exercise (4 times/day, 1-24 days). Basal mRNA expression in sedentary control muscle was inversely related to muscle vascularity. Angiogenesis was histologically evident in trained white gastrocnemius muscle by day 12. Training produced initial three- to sixfold increases in VEGF, VEGF receptors (KDR and Flt), the angiopoietin receptor (Tie-2), and endothelial nitric oxide synthase mRNA, which dissipated before the increase in capillarity, and a substantial (30- to 50-fold) but transient upregulation of monocyte chemoattractant protein 1 mRNA. These results emphasize the importance of early events in regulating angiogenesis. However, we observed a sustained elevation of the angiopoietin 2-to-angiopoietin 1 ratio, suggesting continued vascular destabilization. The response to exercise was (in general) tempered in high-oxidative muscles. These findings place importance on cellular events coupled to the onset of angiogenesis.AJP Heart and Circulatory Physiology 06/2003; 284(5):H1668-78. DOI:10.1152/ajpheart.00743.2002 · 4.01 Impact Factor