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Enhanced endothelin-1-mediated leg vascular tone in healthy older subjects

¹Department of Physiology, Institute of Fundamental and Clinical Movement Sciences, Departments of ²Pharmacology and Toxicology, ³Internal Medicine, and ⁴Cardiology, Radboud University Nijmegen Medical Centre, The Netherlands

Submitted 2 April 2007 ; accepted in final form 5 June 2007

Advanced age is associated with a decreased leg blood flow and reduced physical activity. Endothelin (ET-1), a powerful vasoconstrictor, may play a role in the increased leg vascular tone in older men. OBJECTIVES: to assess the ET-1-mediated vascular tone in the legs of healthy sedentary older men, both before and after 8 wk of exercise training. METHODS: in 8 younger subjects (19–50 yr) and 8 older men (67–76 yr), bilateral leg blood flow was measured using venous occlusion plethysmography before and after antagonizing ET-1 (using selective ET_A/B-receptor antagonists). In older men, reversibility of the observations was assessed after 8 wk of cycling. RESULTS: ET-receptor inhibition increased leg blood flow significantly more in older men compared with younger individuals (29 ± 9% and 10 ± 4%, respectively, P < 0.05). Eight-week cycling training increased baseline blood flow in older men. The blood flow response to ET-receptor inhibition in older men was not affected by the training program (25 ± 8%, P > 0.05 for comparison with pretraining). The flow ratio (blood flows infused leg/noninfused leg) decreased significantly by training from 26 ± 8% to 7+3% (P < 0.05). CONCLUSION: the increased baseline vascular tone in aging is at least in part mediated by the endothelin. Eight-weeks cycling training in older sedentary men decreased leg vascular tone and seems to partly decrease the ET-1-mediated vascular tone.

endothelin; endothelium; exercise; cardiovascular disease

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