LOCAL NEUROGENIC REGULATION OF RAT HINDLIMB CIRCULATION - ROLE OF CALCITONIN-GENE-RELATED PEPTIDE IN VASODILATATION AFTER SKELETAL-MUSCLE CONTRACTION

1 The mechanism of neurogenic regulation of skeletal muscle circulatio n was studied in the hindlimb of anaesthetized rats in vivo. Regional blood flow (RBF) of the hindlimb was recorded with a pulsed Doppler fl ow probe positioned in the iliac artery. 2 A short period (1 min) of s ciatic 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 chang e in either MBP or HR, suggesting that the nerve stimulation produced local vasodilatation of the peripheral vasculature. The hyperaemic res ponse reached a peak within 15 s and characteristically remained above the basal level for more than 5 min after the cessation of nerve stim ulation. The response was regarded as a secondary response brought abo ut by the contraction of skeletal muscles since (+)-tubocurarine (0.73 mu mol kg(-1), i.a.) almost abolished it. 3 Lignocaine (43 mu mol kg( -1), i.a.) and capsaicin (0.33 mu mol kg(-1), i.a.) significantly supp ressed the hyperaemic response to skeletal muscle contraction, suggest ing that capsaicin-sensitive sensory nerves contribute to the hyperaem ia. In contrast, an inhibitor of NO synthase, N-omega-nitro-L-arginine methyl ester (1 mu mol kg(-1) min(-1), i.v.), did not affect the hype raemic response. 4 Serum levels of calcitonin gene-related peptide (CG RP) in iliac venous effluent significantly increased from 51+/-4 to 77 +/-5 fmol ml(-1) during the hyperaemic response to skeletal muscle con traction. 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) (10 0 nmol kg(-1) min(-1), i.v.), a specific CGRP, receptor antagonist, si gnificantly suppressed the hyperaemic response, especially the sustain ed phase of the response which was almost abolished by this antagonist . 5 These results suggest that CGRP, which is released from peripheral endings of capsaicin-sensitive sensory nerves, partly mediates the hy peraemia evoked by skeletal muscle contraction of the rat hindlimb.