Figure 4
From: CGRP signalling inhibits NO production through pannexin-1 channel activation in endothelial cells
The capsaicin-initiated NO signalling inhibition is mediated by CGRP release from perivascular sensory nerves. (A) Relaxation induced by 100 nM ACh in KCl-contracted mesenteric arteries 1 h after capsaicin application (1 µM, 20 min) in the presence of 300 nM CGRP8–37. Vasodilator responses were evaluated in control conditions and after the treatment with 100 µM NG-nitro-L-arginine (L-NA) or 10 µM indomethacin (Indo). (B) NO production induced by ACh (100 nM) observed in mesenteric arterial beds 1 h after the treatment with capsaicin in the presence of 300 nM CGRP8–37 or the vehicle. (C) Representative Western blots and densitometric analysis of eNOS phosphorylation at serine 1177 (P-eNOSSer1177) in mesenteries treated 1 h before with capsaicin (Caps) in the presence of 300 nM CGRP8–37 or the vehicle of capsaicin. (D) Relaxation induced by 100 nM ACh in KCl-contracted resistance arteries of sham and denervated mesenteries before (control) and 15 or 60 min after the treatment with capsaicin (1 µM, 20 min). ACh was applied in the presence of 10 µM indomethacin to prevent the interference of prostaglandins in the response, as shown in the experimental protocol depicted in Fig. 2. (E) Detection of perivascular sensory nerves through immunofluorescence analysis of CGRP expression. Values are means ± SEM. *P < 0.001 vs control by one-way ANOVA plus Dunnett post hoc test. Scale bars represent 100 µm.
