Impaired training-induced adaptation of blood pressure in COPD patients: implication of the muscle capillary bed

Abstract

Background and aimsTargeting the early mechanisms in exercise-induced arterial hypertension (which precedes resting arterial hypertension in its natural history) may improve cardiovascular morbidity and mortality in COPD patients. Capillary rarefaction, an early event in COPD before vascular remodeling, is a potential mechanism of exercise-induced and resting arterial hypertension. Impaired training-induced capillarization was observed earlier in COPD patients; thus, this study compares the changes in blood pressure (BP) during exercise in COPD patients and matches control subjects (CSs) after a similar exercise training program, in relationship with muscle capillarization.MethodsResting and maximal exercise diastolic pressure (DP) and systolic pressure (SP) were recorded during a standardized cardiopulmonary exercise test, and a quadriceps muscle biopsy was performed before and after training.ResultsA total of 35 CSs and 49 COPD patients (forced expiratory volume in 1 second =54%±22% predicted) completed a 6-week rehabilitation program and improved their symptom-limited maximal oxygen uptake (VO2SL: 25.8±6.1 mL/kg per minute vs 27.9 mL/kg per minute and 17.0±4.7 mL/kg per minute vs 18.3 mL/kg per minute; both P<0.001). The improvement in muscle capillary-to-fiber (C/F) ratio was significantly greater in CSs vs COPD patients (+11%±9% vs +23%±21%; P<0.05). Although maximal exercise BP was reduced in CSs (DP: 89±10 mmHg vs 85±9 mmHg; P<0.001/SP: 204±25 mmHg vs 196±27 mmHg; P<0.05), it did not change in COPD patients (DP: 94±14 mmHg vs 97±16 mmHg; P=0.46/SP: 202±27 mmHg vs 208±24 mmHg; P=0.13). The change in muscle C/F ratio was negatively correlated with maximal exercise SP in CSs and COPD patients (r=−0.41; P=0.02).ConclusionCOPD patients showed impaired training-induced BP adaptation related to a change in muscle capillarization, suggesting the possibility of blunted angiogenesis.

Exercise-mediated angiogenesis

“…Interestingly, during healthy aging there appears to be local feedback that coordinates capillary rarefaction in order to preserve appropriate supply to the individual fibre requirements [63]. However, there are a number of pathologies that are accompanied by impaired peripheral microvascular supply that may not maintain this relationship; including COPD [65], CHF [66][67][68], diabetes [30,35,48,69,70], PVD [44] and spinal cord injury (SCI) [71]. This supply-demand mismatch is an obvious candidate driving development of the observed exercise intolerance, and hence exercise-induced angiogenesis would appear to be a worthwhile therapeutic goal.…”

Candidate gene prioritization for chronic obstructive pulmonary disease using expression information in protein–protein interaction networks

“…“Angiogenesis” was observed to be significantly decreased among COPD patients versus controls. This suggested the possibility of blunted “angiogenesis” in COPD patients, who showed impaired training-induced blood pressure adaptation related to a change in muscle capillarizatio [ 34 , 35 ]. Hepatocyte growth factor was involved in the pathogenesis of various lung diseases as it was significantly higher in COPD patients compared to control patients.…”

Distinct structural and functional angiogenic responses are induced by different mechanical stimuli

“…The divergent functional response to different angiogenic stimuli highlights the potential pitfall in pharmacologically induced vascular expansion. Of course, such interpretation comes with the caveat that this experimental work used healthy, young animals; contrasting results may be found after pharmacological expansion of the capillary bed in muscle that exhibits a compromised microcirculation due to diseases like COPD, 44 heart failure 6 or spinal cord injury. 45 In this case, even stochastic vessel growth might prove beneficial in replacing otherwise lost capillaries.…”