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: To test the hypotheses that high tidal-volume ventilation increases plasminogen activator inhibitor (PAI)-1, and the angiotensin-converting enzyme inhibitor, captopril (CAP), may attenuate these effects. University research facility. Twenty adult male Sprague-Dawley rats. All rats were randomized to receive two ventilation strategies for 2 h: 1) a high-volume zero positive end-expiratory pressure (PEEP) (HVZP) group at a tidal volume of 40 mL/kg, a respiratory rate of 25 breaths/min, and an FiO2 of 0.21; and 2) an HVZP + CAP group which received an intraperitoneal injection of CAP (100 mg/kg) 30 min before HVZP ventilation. Another group that was not subjected to ventilation served as the control. Total protein recovered from bronchoalveolar lavage fluid was significantly higher in rats ventilated with the HVZP protocols than in control rats. Rats treated with HVZP ventilation had significantly higher lung angiotensin (ANG) II and PAI-1 messenger RNA expression levels and a higher plasma active PAI-1 level than did the control and HVZP + CAP groups. Lung ANG II levels were positively correlated with plasma PAI-1. Representative lung tissue of the HVZP + CAP group showed mild inflammatory cell infiltration and less hemorrhage and fibrin deposition than did the HVZP group. The HVZP and HVZP + CAP groups had significantly higher lung injury scores than did the control group and rats treated with HVZP + CAP ventilation exhibited significantly lower lung injury scores than did the HVZP group. Mechanical ventilation with a high tidal volume and no PEEP increases alveolar fibrin deposition and systemic PAI-1 activity, which are attenuated by captopril, an angiotensin-converting enzyme inhibitor. These results imply that local ANG II is involved in the pathogenesis of disordered coagulation in ventilator-induced lung injury (VILI) and suggest that the protective mechanism of captopril's attenuation of VILI is related to a reduction in PAI-1.Critical care medicine 06/2008; 36(6):1880-5. DOI:10.1097/CCM.0b013e31817c911d · 6.15 Impact Factor
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ABSTRACT: Physical fitness is closely related to cardiovascular health. We examined the effects of estradiol, angiotensin-converting enzyme inhibitor, exercise training, and their combination on exercise capacity as well as skeletal muscle fiber type and capillarity in old female rats. Twelve-month-old female Wistar-Kyoto rats were allocated to six groups: control (C), treatment with 17 beta-estradiol (0.025 mg/kg/dose, i.p. twice a week) (Est), perindopril (2 mg/kg/day) (Per), exercise training on a treadmill (15 m/min, 10 grade incline, 60 min/day, 5 days/week) (Exe), and combinations of a drug and exercise training (Exe+Est and Exe+Per). Following 6-month interventions, the rats were submitted to a stepwise exercise test on a treadmill. Moreover, fiber type and capillarity in both the soleus and gastrocnemius muscles were examined. Exercise capacity, capillary density, and the percentage of type I fiber significantly increased in Exe, Exe+Est, and Exe+Per compared to C. There were no significant differences in exercise capacity, capillary density, and percentage of type I fiber among C, Est, and Per. The combination of exercise training and perindopril further increased capillary density in both the soleus and gastrocnemius muscles, and the percentage of type I fiber in the gastrocnemius muscle compared to exercise training alone. We found that in old female rats, chronic treatment with estradiol or perindopril affected neither untrained exercise capacity nor exercise capacity acquired as a result of exercise training. However, we found that perindopril promotes adaptive changes of skeletal muscle in response to exercise such as increases in capillary density and the percentage of type I fiber.Clinical and Experimental Hypertension 01/2010; 32(2):76-83. DOI:10.3109/10641960902993046 · 1.46 Impact Factor
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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.