CGRP and nitric oxide of neuronal origin and their involvement in neurogenic vasodilatation in rat skin microvasculature

1 Sensory nerves are important for the initiation of neurogenic inflammation and tissue repair. Both calcitonin gene-related peptide (CGRP) and nitric oxide (NO) have been implicated in neurogenic vasodilatation and inflammatory responses. 2 A blister model in the rat hind footpad was used as a site to induce neurogenic vasodilatation in response to antidromic electrical stimulation of the sciatic nerve. Blood flux was monitored with a laser Doppler flow monitor. 3 The quantitative contributions of CGRP and NO to vasodilatation were examined by use of the CGRP receptor antagonist CGRP(8-37) and NO synthase inhibitors 7-nitroindazole (7-NI), 3-bromo 7-NI and N-G-nitro L-arginine methyl ester (L-NAME). The potential modulatory role of endothelin was examined by use of the ETA receptor antagonist BQ-123. 4 CGRP(8-37) (10 mu M) was perfused over the blister base before nerve stimulation and continuously throughout the post-stimulation period, resulting in a significant reduction (41%) in the blood flux vascular response. 5 Pretreatment with the specific neuronal NO synthase inhibitors, 7-NI and 3-bromo 7-NI (10 mg kg(-1), i.v.), and of the non-specific L-NAME (100 mu M), resulted in significant inhibition of the blood flux response (36%, 72% and 57% decrease, respectively). In contrast, 7-NI treatment in young rats pretreated with capsaicin had no further effect on the vascular response, suggesting that the source of NO is the sensory nerves. 6 BQ-123 (10 mu M) significantly enhanced the stimulation-induced blood Aux response (61% increase). When 7-NI was co-administered with either CGRP(8-37) Or BQ-123, the drug actions were additive, suggesting that there was no interaction between NO and CGRP or endothelin. 7 These data suggest that both NO and CGRP participate in neurogenic vasodilatation in rat skin microvasculature and that this response is modulated by endogenous endothelin.