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Effect of a calcitonin gene‐related peptide antagonist (CGRP 8–37 ) on skin vasodilatation and oedema induced by stimulation of the rat saphenous nerve
Author(s) -
Escott K. Jane,
Brain Susan D.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13878.x
Subject(s) - calcitonin gene related peptide , capsaicin , calcitonin , vasodilation , endocrinology , saphenous nerve , medicine , stimulation , blood flow , prostacyclin , chemistry , antagonist , prostaglandin , neuropeptide , anesthesia , receptor
1 The effect of the calcitonin gene‐related peptide antagonist (CGRP 8–37 , 400 nmol kg −1 , i.v.) on the increased blood flow induced by calcitonin gene related peptide (CGRP), vasodilator prostaglandins, and topical capsaicin was measured with a laser Doppler blood flow meter in rat abdominal skin. 2 The saphenous nerve was electrically stimulated and the effect of CGRP 8–37 (400 nmol kg −1 , i.v.) on the increased blood flow (measured by laser Doppler flowmetry) and oedema formation (measured by the extravascular accumulation of [ 125 I]‐albumin) was investigated in the rat hind paw. 3 CGRP 8–37 (400 nmol kg −1 , i.v.) had no effect on basal cutaneous blood flow at uninjected sites and sites injected with Tyrode buffer, but acted selectively to inhibit the increased blood flow induced by intradermal CGRP (10 pmol/site, P < 0.05), but not that induced by prostaglandin E 2 (PGE 2 , 300 pmol/site) or carba‐prostacyclin (cPGI 2 , 100 pmol/site). 4 Capsaicin (0.1–33 m m ), applied topically, acted in a dose‐related manner to increase blood flow. CGRP 8–37 (400 nmol kg −1 , i.v.) almost totally inhibited blood flow induced by capsaicin (10 m m ; P < 0.05) but did not significantly inhibit blood flow induced by a higher dose of capsaicin (33 m m ). 5 The increased blood flow induced by short stimulation of the saphenous nerve (10 V, 1 ms, 2 Hz for 30 s) was inhibited by 76%, 5 min after i.v. CGRP 8–37 (400 nmol kg −1 , i.V., P < 0.05). 6 A longer (5 min) electrical stimulation of the saphenous nerve caused oedema formation, in addition to increased blood flow. The oedema formation was significantly inhibited by CGRP 8–37 (400 nmol kg −1 , i.v., P < 0.05). 7 The results suggest that the potent microvascular vasodilator neuropeptide, CGRP, is responsible for the increased blood flow observed after short stimulation of the saphenous nerve and that endogenous CGRP contributes in a pro‐inflammatory manner to neurogenic oedema formation in the rat hind paw.