Pharmacological characteristics of the canine cerebrovascular constriction produced by neuropeptide Y.
In order to elucidate the role of neuropeptide Y (NPY) in cerebral circulation, we undertook the present study to examine the action of NPY itself, and the combined effects of NPY with other vasoconstrictor stimuli. NPY itself produced contractions of isolated canine basilar artery in a concentration-dependent manner, which was independent of the presence or absence of endothelium. C-terminal peptides of NPY (NPY12-36) and (NPY22-36) were weak agonists, while those without C-terminals were ineffective. The vasoconstriction produced by NPY was, however, strongly potentiated by increasing the K+ concentration in the medium up to 20 mM, or by pretreatment with tetraethylammonium, a K+ channel blocker and hemolysate containing oxyhemoglobin. NPY also augmented the contractile responses to prostaglandin F2 alpha, norepinephrine, and histamine, but not to serotonin. The contraction in response to NPY per se or in 20 mM K+ was effectively attenuated by Ca2+ antagonists such as d-cis-diltiazem, and in a Ca(2+)-free medium. These results suggest that in canine basilar artery, the activation of the Y1 receptor modulates the availability of the L-type Ca2+ channel, leading to enhance Ca2+ influx from the extracellular space and potentiate contractile effects of other cerebral vasoconstrictors. This might be involved in the cerebral vasospasm which occurs after subarachnoid hemorrhage.
Uneyama
H
H
Department of Pharmacology, University of Shizuoka, School of Pharmaceutical Sciences, Japan.
Tanaka
Y
Y
Iwata
S
S
Ishiguro
T
T
Nakayama
K
K
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000378:metabolism; D001679:Biogenic Amines / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology
D001679:Biogenic Amines; D015220:Calcium Channels; D009478:Neuropeptide Y; D010446:Peptide Fragments; D013757:Tetraethylammonium Compounds; D014665:Vasodilator Agents; D012701:Serotonin; D011189:Potassium Chloride; D006632:Histamine; D015237:Dinoprost