Leg uptake of calcitonin gene-related peptide during exercise in spinal cord injured humans

Exercise-induced increases in cardiac output (CO) and oxygen uptake (VO2) a re tightly coupled, as also in absence of central motor activity and neural feedback from skeletal muscle. Neuromodulators of vascular tone and cardia c function - such as calcitonin gene related peptide (CGRP) - may be of imp ortance. Spinal cord injured individuals (six tetraplegic and four parapleg ic) performed electrically induced cycling (FES) with their paralyzed lower limbs for 29 +/- 2 min to fatigue. Voluntary cycling performed both at VO2 similar to FES and at maximal exercise in six healthy subjects served as c ontrol. In healthy subjects, CGRP in plasma increased only during maximal e xercise (33.8 +/- 3.1 pmol l(-1) (rest) to 39.5 +/- 4.3 (14%, P <0.05)) wit h a mean extraction over the working leg of 10% (P <0.05). Spinal cord inju red individuals had more pronounced increase in plasma CGRP (33.2 +/- 3.8 t o 46.9 +/- 3.6 pmol l(-1), P <0.05), and paraplegic and tetraplegic individ uals increased in average by 23% and 52%, respectively, with a 10% leg extr action in both groups (P <0.05). The exercise induced increase in leg blood flow was 10-12 fold in both spinal cord injured and controls at similar VO 2 (P <0.05), whereas CO increased more in the controls than in spinal man. Heart rate (HR) increased more in paraplegic subjects (67 +/- 7 to 132 +/- 15 bpm) compared with controls and tetraplegics (P <0.05). Mean arterial pr essure (MAP) was unchanged during submaximal exercise and increased during maximal exercise in healthy subjects, but decreased during the last 15 min of exercise in the tetraplegics. It is concluded that plasma CGRP increases during exercise, and that it is taken up by contracting skeletal muscle. T he study did not allow for a demonstration of the origin of the CGRP, but i ts release does not require activation of motor centres. Finally, the more marked increase in plasma CGRP and the decrease in blood pressure during ex ercise in tetraplegic humans may indicate a role of CGRP in regulation of v ascular tone during exercise.