Effect of omega-conotoxin GVIA and omega-agatoxin IVA on the capsaicin-sensitive calcitonin gene-related peptide release and autoregulatory vasodilation in rat pial arteries
Kw. Hong et al., Effect of omega-conotoxin GVIA and omega-agatoxin IVA on the capsaicin-sensitive calcitonin gene-related peptide release and autoregulatory vasodilation in rat pial arteries, J CEREBR B, 19(1), 1999, pp. 53-60
This study assesses the effect of neuronal voltage-sensitive Ca2+ channel b
lockers, omega-conotoxin GVIA (CTX), and omega-agatoxin TVA (AgTX) on the v
asodilation and release of calcitonin gene-related peptide (CGRP), both of
which were induced by either application of capsaicin or acute stepwise hyp
otension. Changes in pial arterial diameter were determined directly throug
h a closed cranial window. The vasodilation of pial artery induced by eithe
r CGRP (0.1 mu mol/L) or capsaicin (0.3 mu mol/L) was significantly inhibit
ed by CGRP(8-37) (0.1 mu mol/L) (P < 0.05 and P < 0.05, respectively). The
autoregulatory vasodilation to acute stepwise hypotension was severely atte
nuated by pretreatment with either CTX or AgTX. When the hypotension was ke
pt for 2, 4, and 10 minutes, the releasable CGRP-like immunoreactivity (CGR
P-LI) level (vehicle, 13.4 +/- 1.5 fmol/mm(2)/30 min) by 10 mu mol/L capsai
cin from the isolated pial arteries was significantly reduced in the 4- and
10-minute hypotension groups (11.3 +/- 1.2 fmol/mm(2)/30 min, P < 0.05, an
d 11.1 +/- 1.5 fmol/mm(2)/30 min, P < 0.05, respectively), but not in 2-min
group. Moreover, the CGRP-LI level released by 10 mu mol/L capsaicin (13.7
+/- 0.9 fmol/mm(2)/30 min) also was significantly depressed by pretreatmen
t with 1 mu mol/L CTX to 10.4 +/- 1.0 fmol/mm(2)/30 min (P < 0.01) and with
0.1 mu mol/L AgTX to 8.7(1.7 fmol/mm(2)/30 min (P < 0.001), as well as by
pretreatment with 10 mu mol/L capsaicin (6.0 +/- 1.6 fmol/mm(2)/30 min, P <
0.001). These results suggest that the neuronal N- and P-type voltage-sens
itive Ca2+ channels are implicated in the release of CGRP from capsaicin-se
nsitive perivascular sensory nerves in response to acute hypotension, and t
hat the released CGRP may contribute to the autoregulatory vasodilation in
the cerebral microcirculation.