Pharmacological Characteristics of the Canine Cerebrovascular Constriction Produced by Neuropeptide Y

• Published in: Biological & pharmaceutical bulletin 1995/04/15, Vol.18(4), pp.501-506
• Main Authors: UNEYAMA, Hisayuki, TANAKA, Yoshio, IWATA, Seinosuke, ISHIGURO, Tsuneo, NAKAYAMA, Koichi
• Format: Article
• Language: English
• Subjects: Animals; Basilar Artery - drug effects; Basilar Artery - metabolism; Biogenic Amines - metabolism; Biological and medical sciences; Blood vessels and receptors; calcium channel antagonist; Calcium Channels - drug effects; Calcium Channels - metabolism; canine basilar artery; Cerebrovascular Circulation - drug effects; contractile potentiation; Dinoprost - pharmacology; Dogs; Female; Fundamental and applied biological sciences. Psychology; Histamine - pharmacology; In Vitro Techniques; Isometric Contraction - drug effects; Male; membrane depolarization; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; neuropeptide Y; Neuropeptide Y - pharmacology; Peptide Fragments - pharmacology; Potassium Chloride - pharmacology; Serotonin - pharmacology; Tetraethylammonium Compounds - pharmacology; Vasoconstriction - drug effects; Vasodilator Agents - pharmacology; Vertebrates: cardiovascular system
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.18.501

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 of 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 F2α, 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 Ca2+-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 extracelullar space and potentiate contractile effects of other cerebral vasoconstrictors. This might be involved in the cerebral vasospasm which occurs after subarachnoid hemorrhage.