Introduction 1997 2002 2006 2+ 1988 1995 2006 2005 2004b 2006 2002 2000 2004 2003 2004a 2006a 1997 1999 2002 2006b 2002 2006c 1988 1987 1997 1996 1997 1991a 1987 1991b 2006 2001 1997 2+ + Materials and methods Tissue preparation n n 2 4 2 4 3 2 4 2 4 3 Functional studies l 100 1987 2α + 2006b c 8–37 2006b c 1 1996 1989 N ω l l 2004a b 2006 2006 + 2006 2001 + v 2+ + Ca Ca 2+ + Ca 2004b 2006 1997 2006 Further, in porcine distal coronary artery, we also studied the effect of repeated administration of capsaicin (50 μM, four times) to verify the reproducibility of the responses in view of possible depletion of endogenous peptide pools or other agents. Measurements of cAMP g Measurements of CGRP in organ bath fluid Human distal coronary artery segments were subjected to a similar protocol as during the functional studies, while bath fluids were collected after construction of the concentration response curve. The bath fluids were collected from the segments treated with vehicle and capsaicin (100 μM), and Krebs solution was used as a control. Bath fluids were stored in tubes containing aprotinin (0.6 TIU/ml) and stored at −80°C. A competitive radioimmunoassay (Peninsula Lab INC., San Carlos, CA, USA) was used according to the instructions of the manufacturer to measure the CGRP concentrations in the bath fluid. Data presentation and statistical analysis + n 50 E max E max 50 B t α (1/n) 2003 P Compounds 8–37 N l Results Functional studies Human arteries n n n 1 1 Fig. 1 Effect of capsaicin or its vehicle in the absence or presence of various pharmacological agents or interventions in precontracted human and porcine distal coronary arteries  Table 1 Effect of various antagonists/interventions on capsaicin-induced relaxations in human isolated artery segments n E max E max 50 50 Human distal coronary artery  (Control) (32) 94 ± 1  5.27 ± 0.12  Olcegepant (1 μM) (10) 89 ± 4 8 ± 4 4.84 ± 0.09 0.33 ± 0.16 8–37 96 ± 3 3 ± 4 4.79 ± 0.06 0.16 ± 0.08 Capsazepine (5 μM) (13) 91 ± 3 1 ± 2 5.10 ± 0.13 0.07 ± 0.16 Ruthenium red (0.1 mM) (9) 92 ± 3 5 ± 3 5.01 ± 0.13 0.21 ± 0.22 L-733060 (5 μM) (7) 94 ± 2 2 ± 2 6.03 ± 0.78 −0.54 ± 0.34 Denuded endothelium (5) 90 ± 6 9 ± 5 5.34 ± 0.48 −0.21 ± 0.58 l 94 ± 2 3 ± 2 5.23 ± 0.48 −0.24 ± 0.45 18-α-Glycyrrhetinic acid (10 μM) (3) 96 ± 2 0 ± 2 5.08 ± 0.28 −0.15 ± 0.38 Olcegepant (1 μM) + L-733060 (5 μM) (3) 90 ± 6 1 ± 3 6.04 ± 0.23 0.06 ± 0.21  (Control) (10) 97 ± 1  5.91 ± 0.32  4-Aminopyridine (1 mM) (6) 95 ± 2 2 ± 3 5.64 ± 0.38 0.94 ± 0.46 Charybdotoxin (0.5 μM) + apamin (0.1 μM) (8) 97 ± 1 0 ± 1 5.80 ± 0.37 0.23 ± 0.37 Iberiotoxin (0.5 μM) + apamin (0.1 μM) (5) 96 ± 2 0 ± 2 5.94 ± 0.65 0.15 ± 0.38 Y-276323 (1 μM) (3) 99 ± 1 −1 ± 2 5.39 ± 0.21 −0.58 ± 0.14 Y-276323 (1 μM) + 4-Aminopyridine (1 mM) (3) 100 ± 0 −3 ± 4 5.12 ± 0.18 0.33 ± 0.28 Human proximal coronary artery  (Control) (4)   34 ± 14 4.30 ± 0.14 Olcegepant (1 μM) (4)   36 ± 16 4.40 ± 0.17 Human meningeal artery  (Control) (10) 91 ± 5   5.04 ± 0.09  Olcegepant (1 μM) (10) 96 ± 1 −5 ± 4 5.03 ± 0.07 −0.07 ± 0.08 Capsazepine (5 μM) (4) 81 ± 9 8 ± 7 4.90 ± 0.31 0.11 ± 0.31 Ruthenium red (0.1 mM) (3) 74 ± 15 5 ± 14 5.13 ± 0.42 0.02 ± 0.62 L-733060 (5 μM) (4) 79 ± 12 8 ± 15 4.80 ± 0.31 −0.09 ± 0.31 E max 50 50 50 8–37 1 1 1 l 1 + 2+ 1 50 50 P 50 n 50 n 1 Porcine arteries n n n n 2 l 1 2 1 2 Table 2 Effect of various antagonists/interventions on capsaicin-induced relaxations in porcine isolated artery segments n E max E max 50 50 Porcine distal coronary artery  (Control) (56) 96 ± 1  5.27 ± 0.09  Olcegepant (1 μM) (10) 92 ± 2 3 ± 2 5.26 ± 0.11 −0.02 ± 0.11 8–37 97 ± 3 −2 ± 5 4.78 ± 0.06 0.00 ± 0.03 Capsazepine (5 μM) (7)  99 ± 1 −3 ± 2 5.15 ± 0.26 0.26 ± 0.16 Ruthenium red (0.1 mm) (12) 88 ± 3 7 ± 4 4.89 ± 0.09 0.47 ± 0.23 L-733060 (5 μM) (7) 88 ± 3 4 ± 4 4.89 ± 0.09 −0.04 ± 0.15 Denuded endothelium (9) 91 ± 4 2 ± 2 5.62 ± 0.49 0.21 ± 0.16 l 90 ± 8 8 ± 8 4.84 ± 0.15 0.28 ± 0.31  (Control) (15) 99 ± 0  5.08 ± 0.15  18-α-Glycyrrhetinic acid (10 μM) (3) 99 ± 1 0 ± 1 5.73 ± 0.75 −0.59 ± 0.53 4-Aminopyridine (1 mM) (7) 96 ± 2 3 ± 2 4.84 ± 0.15 −0.46 ± 0.35 Charybdotoxin (0.5 μM) + apamin (0.1 μM) (11) 99 ± 1 0 ± 1 5.27 ± 0.15 −0.04 ± 0.20 Y-276323 (1 μM) (9) 96 ± 2 3 ± 2 5.17 ± 0.19 0.04 ± 0.21 Y-276323 (1 μM) + 4-Aminopyridine (1 mM) (8) 96 ± 3 4 ± 3 5.22 ± 0.20 0.00 ± 0.11 Porcine proximal coronary artery  (Control) (4) 100 ± 0  5.33 ± 0.42  Olcegepant (1 μM) (4) 90 ± 6  5.79 ± 0.16  Porcine basilar artery  (Control) (3) 97 ± 1  4.70 ± 0.05  Olcegepant (1 μM) (3) 100 ± 0  4.97 ± 0.24  Capsazepine (5 μM) (3)  100 ± 0  4.80 ± 0.01  Porcine meningeal artery  (Control) (3) 99 ± 1  4.82 ± 0.02  Olcegepant 1 μM (3) 99 ± 1  4.88 ± 0.04  E max 50 50 50 Fig. 2 Effect of four consecutive challenges to capsaicin (50 μM) in porcine distal coronary arteries precontracted with KCl (30 mM)  E max 50 n E max 50 n Measurements of cAMP 3 Fig. 3 n n P  Measurements of CGRP levels in organ bath fluid 4 Fig. 4 P  Discussion In the present study, we investigated the role of CGRP in capsaicin-induced relaxations in human and porcine isolated arteries. In all arteries investigated, there does not seem to be any relevant role of CGRP in the relaxant responses to capsaicin. Further, the effects of capsaicin appear to be mediated by non-specific mechanisms. 1991a 2006 8–37 1989 1991b 8–37 1991b 2006c 1991a 1991a 2002 2004 1 50 2006c 1991a 1997 + 2001 1997 + + 2001 2006 Ca Ca 1997 Ca 2006 2001 1990 + l S 2004b 2001 1997 2001 2+ +