[Participation of neuropeptide Y Y3-receptor subtype in the increase in lung vascular permeability--for therapy of respiratory failure].
In order to find some treatments for respiratory failure caused by pulmonary edema, we investigated the mechanism of neurogenic pulmonary edema. Previously, stimulation of sympathetic nerves caused an increase in pulmonary vascular permeability, possibly due to neuropeptide Y. Neuropeptide Y injected into the trachea increased lung vascular permeability dose-dependently, the ED50 of which was 0.3-1 nM. Such an effect remained even after treatment with reserpine, as well as in the presence of alpha- and beta-blockers. And norepinephrine enhanced the effect of neuropeptide Y on lung vascular permeability. These responses were almost similar to those obtained by stimulation of sympathetic nerves. Furthermore, neuropeptide Y, in fibrin-induced pulmonary edema, was localized in alveolar macrophages and alveolar spaces, amounting to approximately 200 nM in edema fluid. The value was significantly greater than that obtained in hydrostatic pulmonary edema by 10-30 times. Peptide YY, an analogue of neuropeptide Y, had no action on lung vascular permeability, whereas the effect of neuropeptide Y was inhibited by pretreatment with neuropeptide Y- 13-36, an antagonist for Y3-recetor subtype. These results suggested that neuropeptide Y enhances the lung vascular permeability via Y3-recetor subtype. Neuropeptide Y- 13-36, in fibrin-induced pulmonary edema, decreased a ratio of protein concentration in edema fluid to that in serum, indicating that neuropeptide Y actually acts a role in the development of neurogenic pulmonary edema, via an increase in lung vascular permeability.
Ishikawa
N
N
Department of Pharmacology, Aichi Medical University School of Medicine, Japan.
Hamdy
O
O
Maekawa
H
H
Murakami
H O
HO
Nishiwaki
K
K
Shimada
Y
Y
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005337:Fibrin; D009478:Neuropeptide Y / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009638:Norepinephrine / Q000494:pharmacology; D019894:Peptide YY / Q000494:pharmacology; D011652:Pulmonary Circulation / Q000187:drug effects; D011654:Pulmonary Edema / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D018013:Receptors, Neuropeptide / Q000037:antagonists & inhibitors / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology; D012131:Respiratory Insufficiency / Q000188:drug therapy*
D018759:Adrenergic Uptake Inhibitors; D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D009478:Neuropeptide Y; D018013:Receptors, Neuropeptide; C106657:neuropeptide Y3 receptor; D019894:Peptide YY; D012110:Reserpine; D005337:Fibrin; D009638:Norepinephrine