PHARMACOLOGICAL CHARACTERISTICS OF THE CANINE CEREBROVASCULAR CONSTRICTION PRODUCED BY NEUROPEPTIDE-Y

In order to elucidate the role of neuropeptide Y (NPY) in cerebral cir culation, we undertook the present study to examine the action of NPY itself, and the combined effects of NPY with other vasoconstrictor sti muli. NPY itself produced contractions of isolated canine basilar arte ry in a concentration-dependent manner, which was independent of the p resence or absence of endothelium. C-terminal peptides of NPY (NPY12-3 6) and (NPY22-36) were weak agonists, while those without C-terminals were ineffective. The vasoconstriction produced by NPY was, however, s trongly potentiated by increasing the K+ concentration in the medium u p to 20 mM, or by pretreatment with tetraethylammonium, a K+ channel b locker and hemolysate containing oxyhemoglobin. NPY also augmented the contractile responses to prostaglandin F-2 alpha, norepinephrine, and histamine, but not to serotonin. The contraction in response to NPY p er se or in 20 mM K+ was effectively attenuated by Ca2+ antagonists su ch as d-cis-diltiazem, and in a Ca2+-free medium. These results sugges t that in canine basilar artery, the activation of the Y-1 receptor mo dulates the availability of the L-type Ca2+ channel, leading to enhanc e Ca2+ influx from the extracelullar space and potentiate contractile effects of other cerebral vasoconstrictors. This might be involved in the cerebral vasospasm which occurs after subarachnoid hemorrhage.