Responsiveness of canine bronchial vasculature to excitatory stimuli and to cooling.
Changes in bronchial vascular tone, in part due to cooling during ventilation, may contribute to altered control of airflow during airway inflammation, asthma, and exercise-induced bronchoconstriction. We investigated the responses of canine bronchial vasculature to excitatory stimuli and cooling. Electrical stimulation evoked contractions in only some (8 of 88) tissues; these were phentolamine sensitive and augmented by N(omega)-nitro-L-arginine. However, sustained contractions were evoked in all tissues by phenylephrine [concentration evoking a half-maximal response (EC(50)) approximately 2 microM] or the thromboxane A(2) mimetic U-46619 (EC(50) approximately 5 nM) and less so by beta,gamma-methylene-ATP or histamine. Cooling to room temperature markedly suppressed ( approximately 75%) adrenergic responses but had no significant effect against U-46619 responses. Adrenergic responses, but not those to U-46619, were accompanied by an increase in intracellular Ca(2+) concentration. Chelerythrine (protein kinase C antagonist) markedly antagonized adrenergic responses (mean maxima reduced 39% in artery and 86% in vein) but had no significant effect against U-46619, whereas genistein (a nonspecific tyrosine kinase inhibitor) essentially abolished responses to both agonists. We conclude that cooling of the airway wall dramatically interferes with adrenergic control of bronchial perfusion but has little effect on thromboxane-mediated vasoconstriction.
Janssen
L J
LJ
Asthma Research Group, Firestone Institute for Respiratory Health, St. Joseph's Hospital and Department of Medicine, McMaster University, Hamilton, Ontario, Canada L8N 3Z5. janssenl@mcmaster.ca
Lu-Chao
H
H
Netherton
S
S
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001980:Bronchi / Q000098:blood supply*; D001981:Bronchial Arteries / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D003080:Cold Temperature; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D066298:In Vitro Techniques; D019335:Nitroarginine / Q000494:pharmacology; D010646:Phentolamine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D014132:Trachea / Q000098:blood supply; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014680:Veins / Q000187:drug effects / Q000502:physiology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D019335:Nitroarginine; C005147:5'-adenylyl (beta,gamma-methylene)diphosphonate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium; D010646:Phentolamine