OBJECTIVE: In vitro studies suggest that the vasodilator mechanism of action of calcitonin gene-related peptide (CGRP) involves various endothelium-dependent and endothelium-independent mechanisms. An in vivo analysis of the contribution of nitric oxide, prostaglandins, calcium-sensitive potassium channels (K(+)(Ca) channels), and adenosine triphosphate (ATP)-sensitive potassium channels (K(+)(ATP) channels) to CGRP-induced vasodilation in humans was performed. METHODS: CGRP (3, 10, and 30 ng x min(-1) x dL(-1) forearm) was infused into the brachial artery of 40 healthy subjects. Forearm vascular responses were measured by venous occlusion plethysmography. First, dose-response curves were constructed during coinfusion of CGRP with placebo (sodium chloride, 0.9%). After washout, in 5 subgroups (n = 8 each), the infusions of CGRP were repeated with placebo (time-control experiments), N(G)-monomethyl-L-arginine (L-NMMA, a nitric oxide-synthase inhibitor), indomethacin (a cyclooxygenase inhibitor), tetraethylammonium chloride (TEAC) (a K(+)(Ca)-channel blocker), and glyburide (INN, glibenclamide) (a K(+)(ATP)-channel blocker), respectively. RESULTS: CGRP induced a dose-dependent and reproducible decrease in forearm vascular resistance (P < .001). Compared with placebo, L-NMMA reduced the decrease in forearm vascular resistance induced by CGRP (P < .001) (3 and 10 ng x min(-1) x dL(-1) forearm). The absence of an inhibitory effect of L-NMMA on CGRP-induced vasodilation at the highest dose of CGRP suggests that still other mechanisms are involved. The vasodilator response to CGRP was not affected by coinfusion of indomethacin, tetraethylammonium chloride, or glyburide. CONCLUSIONS: The intrabrachial infusion of CGRP results in a dose-dependent and reproducible forearm vasodilator response. CGRP-induced vasodilation is dependent at least in part on the release of nitric oxide and does not involve the release of prostaglandins or the activation of K(+)(Ca) channels or K(+)(ATP) channels in humans.
OBJECTIVE: In vitro studies suggest that the vasodilator mechanism of action of calcitonin gene-related peptide (CGRP) involves various endothelium-dependent and endothelium-independent mechanisms. An in vivo analysis of the contribution of nitric oxide, prostaglandins, calcium-sensitive potassium channels (K(+)(Ca) channels), and adenosine triphosphate (ATP)-sensitive potassium channels (K(+)(ATP) channels) to CGRP-induced vasodilation in humans was performed. METHODS:CGRP (3, 10, and 30 ng x min(-1) x dL(-1) forearm) was infused into the brachial artery of 40 healthy subjects. Forearm vascular responses were measured by venous occlusion plethysmography. First, dose-response curves were constructed during coinfusion of CGRP with placebo (sodium chloride, 0.9%). After washout, in 5 subgroups (n = 8 each), the infusions of CGRP were repeated with placebo (time-control experiments), N(G)-monomethyl-L-arginine (L-NMMA, a nitric oxide-synthase inhibitor), indomethacin (a cyclooxygenase inhibitor), tetraethylammonium chloride (TEAC) (a K(+)(Ca)-channel blocker), and glyburide (INN, glibenclamide) (a K(+)(ATP)-channel blocker), respectively. RESULTS:CGRP induced a dose-dependent and reproducible decrease in forearm vascular resistance (P < .001). Compared with placebo, L-NMMA reduced the decrease in forearm vascular resistance induced by CGRP (P < .001) (3 and 10 ng x min(-1) x dL(-1) forearm). The absence of an inhibitory effect of L-NMMA on CGRP-induced vasodilation at the highest dose of CGRP suggests that still other mechanisms are involved. The vasodilator response to CGRP was not affected by coinfusion of indomethacin, tetraethylammonium chloride, or glyburide. CONCLUSIONS: The intrabrachial infusion of CGRP results in a dose-dependent and reproducible forearm vasodilator response. CGRP-induced vasodilation is dependent at least in part on the release of nitric oxide and does not involve the release of prostaglandins or the activation of K(+)(Ca) channels or K(+)(ATP) channels in humans.
Authors: Milena De Felice; Michael H Ossipov; Ruizhong Wang; Gregory Dussor; Josephine Lai; Ian D Meng; Juliana Chichorro; John S Andrews; Suman Rakhit; Shawn Maddaford; David Dodick; Frank Porreca Journal: Brain Date: 2010-07-13 Impact factor: 13.501
Authors: Bart J Van der Schueren; Rebecca Blanchard; M Gail Murphy; John Palcza; Inge De Lepeleire; Anne Van Hecken; Marleen Depré; Jan N de Hoon Journal: Br J Clin Pharmacol Date: 2011-05 Impact factor: 4.335
Authors: Simon R Sinclair; Stefanie A Kane; Bart J Van der Schueren; Alan Xiao; Kenneth J Willson; Janet Boyle; Inge de Lepeleire; Yang Xu; Lisa Hickey; William S Denney; Chi-Chung Li; John Palcza; Floris H M Vanmolkot; Marleen Depré; Anne Van Hecken; M Gail Murphy; Tony W Ho; Jay N de Hoon Journal: Br J Clin Pharmacol Date: 2010-01 Impact factor: 4.335
Authors: Sebastião R Ferreira-Filho; Anna Carolina C R Ferreira; Paulo C Oliveira; Jorge F M Moreira; Eduardo C Ribeiro; Angela M M Oliveira; Maria B do Vale Journal: J Clin Hypertens (Greenwich) Date: 2009-05 Impact factor: 3.738