Neuropeptide Y inhibits neurogenic inflammation in guinea pig airways.
We examined the effect of neuropeptide Y (NPY) on neurogenic airway microvascular leakage. Male Dunkin-Hartley guinea pigs (250-350 g) were anesthetized with urethan (2 g/kg ip). The cervical artery and vein were cannulated for monitoring blood pressure and injecting drugs, respectively. Atropine and propranolol (each 1 mg/kg i.v.) were administered 30 min before the experiment. After pretreatment with saline (vehicle for NPY) or NPY (1-100 micrograms/kg i.v.), Evans blue dye (30 mg/kg iv) was administered. Then, bilateral vagal nerves were electrically stimulated (5 V, 7 Hz, 5-ms duration for 3 min) to induce airway plasma leakage. Airways were divided into four sections [trachea (Tr), main bronchi, central intrapulmonary airways (IPA), and peripheral IPA] and incubated in formamide (37 degrees C for 16 h). The concentration of Evans blue dye was measured by spectrophotometer. Furthermore, we examined the effect of NPY on exogenous substance P- (0.3 microgram/kg i.v.) induced plasma extravasation. Bilateral vagal stimulation significantly increased leakage of dye in Tr to peripheral IPA. NPY did not affect basal leakage but did significantly inhibit neurogenic plasma extravasation in a dose-dependent manner with maximal inhibitions of 42.3 (Tr), 67.7 (main bronchi), 38.2 (central IPA), and 26.3% (peripheral IPA) at 30 micrograms/kg. Exogenous substance P-induced plasma extravasation was not inhibited by NPY. We conclude that NPY inhibits neurogenic inflammation by prejunctional inhibition of neuropeptide release from airway sensory nerve terminals.
Takahashi
T
T
First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan.
Ichinose
M
M
Yamauchi
H
H
Miura
M
M
Nakajima
N
N
Ishikawa
J
J
Inoue
H
H
Takishima
T
T
Shirato
K
K
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001341:Autonomic Nervous System / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007249:Inflammation / Q000503:physiopathology*; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D010276:Parasympatholytics / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D012137:Respiratory System / Q000503:physiopathology*; D013373:Substance P / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D009478:Neuropeptide Y; D010276:Parasympatholytics; D013373:Substance P