Local neurogenic regulation of rat hindlimb circulation: role of calcitonin gene‐related peptide in vasodilatation after skeletal muscle contraction

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Abstract
The mechanism of neurogenic regulation of skeletal muscle circulation was studied in the hindlimb of anaesthetized rats in vivo. Regional blood flow (RBF) of the hindlimb was recorded with a pulsed Doppler flow probe positioned in the iliac artery. A short period (1 min) of sciatic nerve stimulation at 10 Hz caused a sustained increase in RBF (from 2.0±0.2 to 3.7±0.2 kHz at the peak), but no appreciable change in either MBP or HR, suggesting that the nerve stimulation produced local vasodilatation of the peripheral vasculature. The hyperaemic response reached a peak within 15 s and characteristically remained above the basal level for more than 5 min after the cessation of nerve stimulation. The response was regarded as a secondary response brought about by the contraction of skeletal muscles since (+)‐tubocurarine (0.73 μmol kg−1, i.a.) almost abolished it. Lignocaine (43 μmol kg−1, i.a.) and capsaicin (0.33 μmol kg−1, i.a.) significantly suppressed the hyperaemic response to skeletal muscle contraction, suggesting that capsaicin‐sensitive sensory nerves contribute to the hyperaemia. In contrast, an inhibitor of NO synthase, Nω‐nitro‐L‐arginine methyl ester (1 μmol kg−1 min−1, i.v.), did not affect the hyperaemic response. Serum levels of calcitonin gene‐related peptide (CGRP) in iliac venous effluent significantly increased from 51±4 to 77±5 fmol ml−1 during the hyperaemic response to skeletal muscle contraction. A bolus injection of CGRP (300 pmol kg−1, i.a.) induced a long‐lasting increase in RBF of the hindlimb. Moreover, CGRP(8–37) (100 nmol kg−1 min−1, i.v.), a specific CGRP1 receptor antagonist, significantly suppressed the hyperaemic response, especially the sustained phase of the response which was almost abolished by this antagonist. These results suggest that CGRP, which is released from peripheral endings of capsaicin‐sensitive sensory nerves, partly mediates the hyperaemia evoked by skeletal muscle contraction of the rat hindlimb. British Journal of Pharmacology (1997) 122, 703–709; doi:10.1038/sj.bjp.0701422