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.
This study assesses the effect of neuronal voltage-sensitive Ca2+ channel blockers, omega-conotoxin GVIA (CTX), and omega-agatoxin IVA (AgTX) on the vasodilation and release of calcitonin gene-related peptide (CGRP), both of which were induced by either application of capsaicin or acute stepwise hypotension. Changes in pial arterial diameter were determined directly through a closed cranial window. The vasodilation of pial artery induced by either CGRP (0.1 micromol/L) or capsaicin (0.3 micromol/L) was significantly inhibited by CGRP(8-37) (0.1 micromol/L) (P < 0.05 and P < 0.05, respectively). The autoregulatory vasodilation to acute stepwise hypotension was severely attenuated by pretreatment with either CTX or AgTX. When the hypotension was kept for 2, 4, and 10 minutes, the releasable CGRP-like immunoreactivity (CGRP-LI) level (vehicle, 13.4+/-1.5 fmol/mm2/30 min) by 10 micromol/L capsaicin from the isolated pial arteries was significantly reduced in the 4- and 10-minute hypotension groups (11.3+/-1.2 fmol/mm2/30 min, P < 0.05, and 11.1+/-1.5 fmol/mm2/30 min, P < 0.05, respectively), but not in 2-min group. Moreover, the CGRP-LI level released by 10 micromol/L capsaicin (13.7+/-0.9 fmol/mm2/30 min) also was significantly depressed by pretreatment with 1 micromol/L CTX to 10.4+/-1.0 fmol/mm2/30 min (P < 0.01) and with 0.1 micromol/L AgTX to 8.7(1.7 fmol/mm2/30 min (P < 0.001), as well as by pretreatment with 10 micro-mol/L capsaicin (6.0+/-1.6 fmol/ mm2/30 min, P < 0.001). These results suggest that the neuronal N- and P-type voltage-sensitive Ca2+ channels are implicated in the release of CGRP from capsaicin-sensitive perivascular sensory nerves in response to acute hypotension, and that the released CGRP may contribute to the autoregulatory vasodilation in the cerebral microcirculation.
Hong
K W
KW
Department of Pharmacology, College of Medicine, Pusan National University, Korea.
Kim
C D
CD
Rhim
B Y
BY
Lee
W S
WS
D000818:Animals; D019898:Autocrine Communication / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002211:Capsaicin / Q000494:pharmacology; D002536:Cerebral Arteries / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D002540:Cerebral Cortex / Q000098:blood supply*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects*; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA
D002121:Calcium Channel Blockers; D010455:Peptides; D013111:Spider Venoms; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D002118:Calcium