- 1The 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.
- 2A 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.
- 3Lignocaine (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.
- 4Serum 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.
- 5These 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