It has been established by early investigations that sensory nerves are involved in cutaneous inflammatory responses including vasodilation and plasma protein extravasation. These effects have been considered to be due to the release of substance P (SP) from local sensory terminals close to blood vessels since an SP analogue with tachykinin antagonistic activity blocked both neurogenic vasodilation and plasma extravasation in the skin (Lembeck et al. 1982). Recently, specific neurokinin 1 (NK1) antagonists of a non-peptide nature have been developed and initial studies showed that neurogenic plasma protein extravasation was indeed abolished by the compound RP-67.580 (Garret et al. 1991) in agreement with SP being the mediator. Since the capsaicin-sensitive sensory nerves also contain another potent vasodilator in addition to SP, namely calcitonin gene-related peptide (CGRP) (Lundberg et al. 1985) and the effect of this peptide can be blocked by the CGRP fragment CGRP(8-37) (Chiba et al. 1989), we initiated the present study to determine the relative involvement of S P and CGRP mechanisms in the vasodilatory response to an tidromic nerve stimulation in rat skin.Male Sprague-Dawley rats (25C300 g) were pretreated with guanethidine chloride (20 mg kg-l s.c., Ciba-Geigy, Basel, Switzerland) one day prior to the experiment to impair the effecrj of concomitant stimulation of sympathetic axons in the saphenous nerve (Gamse & Saria 1987). Arterial blood pressure was monitored via a carotid arterial catheter and drugs were injected via the jugular vein. The distal end of the saphenous nerve was stimulated with 20 impulses ( 2 Hz, 10 V, 1 ms, for 10 s) with 30-min intervals.The flux of blood cells was recorded using a Perimed laser Doppler flow meter (Perimed, Stockholm, Sweden) as an indication of cutaneous blood flow (LDF signal) at the medio-dorsal side of the skin of the hindpaw, i.e. at the region innervated by the saphenous nerve. Alpha-CGRP(8-37) (human) and a-CGRP (rat) and SP (Peninsula, Merseyside, UK) were dissolved in saline and RP-67.580 (Rh6ne-Poulenc Rorer, Vitry-sur-Seine, France) was initially dissolved (1 Yn w : v) in hydrochloric acid and diluted further with saline. Data were expressed as mean$SEM and given as area under the curve (AUC) compared to base line. Statistical significance was determined by the Dunnett test.Antidromic stimulation of the saphenous nerve at 2 Hz, for 10 s, led to an increase of LDF readings by 103+ 20?& without changing blood pressure. The effect did not reach maximum until 1 min after the stimulation was turned off and lasted for at least 5 min. Pretreatment with RP-67.580 (1 mg kg-' i.v., 5 min before the stimulation) did not change the basal blood pressure or L D F recordings. A slight but nonsignificant increase of the response to saphenous nerve stimulation was observed after RP-67.580 pretreatment (Fig. 1). After pretreatment with CGRP(8-37) (0.3 mg kg-' i.v., 3 min before the stimulation), basal readings were not changed while the integrated L D F increase to antidrom...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.