title: Dilation of rat diaphragmatic arterioles by flow and hypoxia: roles of nitric oxide and prostaglandins.
abstract: The in vitro responses to ACh, flow, and hypoxia were studied in arterioles isolated from the diaphragms of rats. The endothelium was removed in some vessels by low-pressure air perfusion. In endothelium-intact arterioles, pressurized to 70 mmHg in the absence of luminal flow, ACh (10(-5) M) elicited dilation (from 103 +/- 10 to 156 +/- 13 microm). The response to ACh was eliminated by endothelial ablation and by the nitric oxide synthase antagonists NG-nitro-L-arginine (L-NNA; 10(-5) M) and NG-nitro-L-arginine methyl ester (L-NAME, 10(-5) M) but not by indomethacin (10(-5) M). Increases in luminal flow (5-35 microl/min in 5 microl/min steps) at constant distending pressure (70 mmHg) elicited dilation (from 98 +/- 8 to 159 +/- 12 microm) in endothelium-intact arterioles. The response to flow was partially inhibited by L-NNA, L-NAME, and indomethacin and eliminated by endothelial ablation and by concurrent treatment with L-NAME and indomethacin. The response to hypoxia was determined by reducing the periarteriolar PO2 from 100 to 25-30 Torr by changing the composition of the gas used to bubble the superfusing solution. Hypoxia elicited dilation (from 110 +/- 9 to 165 +/- 12 microm) in endothelium-intact arterioles but not in arterioles from which the endothelium had been removed. Hypoxic vasodilation was eliminated by treatment with indomethacin and was not affected by L-NAME or L-NNA. In rat diaphragmatic arterioles, the response to ACh is dependent on endothelial nitric oxide release, whereas the response to hypoxia is mediated by endothelium-derived prostaglandins. Flow-dilation requires that both nitric oxide and cyclooxygenase pathways be intact.
authors.affiliation: Divisions of Pulmonary and Critical Care Medicine, Royal Victoria Hospital and Meakins-Christie Laboratories, McGill University, Montreal, Quebec, Canada H2X 2P2. mward@meakins.lan.mcgill.ca
authors.forename: M E
authors.initials: ME
authors.lastname: Ward
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001160:Arterioles / Q000502:physiology; D003964:Diaphragm / Q000098:blood supply*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D010101:Oxygen Consumption / Q000187:drug effects; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000502:physiology; D014664:Vasodilation / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin