Evidence that calcitonin gene-related peptide contributes to the capsaicin-induced relaxation of guinea pig cerebral arteries.
Pretreatment with capsaicin caused a depletion of substance P (SP)-, neurokinin A (NKA)- and calcitonin gene-related peptide (CGRP)-like immunoreactivity (-LI) from the trigeminal ganglion, dura mater and cerebral arteries. The effect of capsaicin on isolated basilar arteries of guinea pig resulted in a biphasic relaxant response of histamine precontracted vessels. The first phase of the capsaicin-induced relaxation was absent in capsaicin-treated guinea pigs. Furthermore, repeated administration of capsaicin decreased the first but not the second phase of relaxation, supporting the view that a stored agent was released, while the second phase probably was due to a direct effect of capsaicin per se. The biphasic effect was not modified by the SP antagonist Spantide in a concentration that blocks tachykinin response (3.10(-6) M), nor by removal of the endothelium. There was no significant difference in pD2 values (-log concentration eliciting half maximum relaxation) between relaxations induced by SP, NKA, neurokinin B, neuropeptide K or CGRP in capsaicin pretreated as compared to vehicle-treated animals. These results are in support of the assumption that CGRP is involved in the capsaicin-induced relaxation caused by release of vasoactive agents from sensory afferent nerves.
Jansen
I
I
Department of Experimental Research, Malmö General Hospital, Sweden.
Alafaci
C
C
Uddman
R
R
Edvinsson
L
L
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D002211:Capsaicin / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000502:physiology*; D006168:Guinea Pigs; D007150:Immunohistochemistry; D009126:Muscle Relaxation; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D015288:Neurokinin A / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D014664:Vasodilation
D013373:Substance P; D015288:Neurokinin A; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin