Analysis of gamma-aminobutyric acid-mediated responses in the pulmonary vascular bed of the cat.
In this investigation, we sought to identify the role of gamma-aminobutyric acid (GABA)(A) and GABA(B) receptors in the feline pulmonary vascular bed. Using adult mongrel cats and in separate experiments, we investigated the effects of l-N(5)-(1-iminoethyl) ornithine hydrochloride (l-NIO) (a nitric oxide synthase inhibitor), glibenclamide (an adenosine triphosphate (ATP)-sensitive K(+) channel blocker), meclofenamate (a nonselective cyclooxygenase inhibitor), bicuculline (a GABA(A) receptor antagonist), and saclofen (a GABA(B) receptor antagonist) on pulmonary arterial responses to pinacidil (an ATP-sensitive K(+) channel activator), bradykinin (a nitric oxide synthase inducer), muscimol (a GABA(A) receptor agonist), and 3-aminopropyl(methyl)phosphinic acid, hydrochloride (SKF-97541; a GABA(B) receptor agonist). Under increased tone conditions in the isolated left lower lobe vascular bed of the cat, muscimol induced a dose-dependent vasodepressor response that was not significantly altered after the administration of l-NIO, glibenclamide, meclofenamate, and saclofen. SKF-97541-induced vasodepression was not significantly attenuated after the administration of l-NIO, meclofenamate, and bicuculline. Responses to SKF-97541 were significantly attenuated after the administration of glibenclamide and saclofen. Responses to muscimol were significantly reduced after the administration of bicuculline. The results suggest that muscimol and SKF-97541 have potent vasodepressor activity in the feline pulmonary vascular bed and that these responses are modulated by, respectively, GABA(A) and GABA(B) receptor-sensitive pathways. Further, SKF-97541-induced vasodepression is mediated or modulated by an ATP-sensitive K(+) channel.
Kaye
Alan D
AD
Department of Anesthesiology, Texas Tech University Health Sciences, 3601 4th Street, Room 1C282, Lubbock, TX 79430, USA. alan.kaye@ttuhsc.edu
Hoover
Jason M
JM
Baber
Syed R
SR
Ibrahim
Ikhlass N
IN
Fields
Aaron M
AM
D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives* / Q000494:pharmacology; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology; D002415:Cats; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D008168:Lung / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011963:Receptors, GABA-A / Q000502:physiology*; D018080:Receptors, GABA-B / Q000502:physiology*
D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C068457:3-aminopropyl(methyl)phosphinic acid; D008469:Meclofenamic Acid; D001418:Baclofen; C080629:saclofen; D005905:Glyburide