title: PGD2 is an intermediate in agonist-stimulated nitric oxide release in rabbit skin microcirculation.
abstract: We investigated the role of endogenous prostaglandins and NO in the blood flow response of skin microcirculation in vivo. Test agents were injected intradermally in anesthetized rabbits and changes in skin blood flow measured with a laser-Doppler flow probe. Skin blood flow increased 75% at 7.33, 6.77, 11.63, 10.30, 10.55, 8.20, and < 7 -log mol/site with acetylcholine, ATP, bradykinin, prostaglandin D2 (PGD2), prostaglandin E2 (PGE2), NO gas in solution, and nitroprusside respectively. Co-injection of indomethacin (3 x 10(-9) mol/site) or NG-nitro-L-arginine methyl ester (L-NAME; 10(-7) mol/site) with either acetylcholine or bradykinin abolished the effects. This suggests a link between NO and prostaglandin release. Arachidonic acid increased blood flow, which was inhibited by indomethacin, L-NAME, or the PGD2-receptor antagonist BW-A868C. Blood flow responses to either intradermal acetyl-choline or bradykinin, but not to NO in solution, were abolished by co-injection with BW-A868C. PGD2-mediated vasodilation was abolished by L-NAME or BW-A868C, but not by indomethacin. There was no evidence of a link between NO and prostaglandin release in precontracted rabbit aortic rings in vitro. The results suggest that, in the microcirculation of rabbit skin, acetylcholine- and bradykinin-mediated vasodilation involve the arachidonic acid-PGD2-NO pathway.
authors.affiliation: Department of Applied Pharmacology, National Heart and Lung Institute, London, United Kingdom.
authors.forename: J B
authors.initials: JB
authors.lastname: Warren
authors.forename: R K
authors.initials: RK
authors.lastname: Loi
authors.forename: A J
authors.initials: AJ
authors.lastname: Wilson
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D006827:Hydantoins / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D008955:Models, Cardiovascular; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000494:pharmacology / Q000502:physiology*; D019001:Nitric Oxide Synthase; D009599:Nitroprusside / Q000494:pharmacology; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000494:pharmacology / Q000502:physiology*; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*
chemical_list: D006827:Hydantoins; D010975:Platelet Aggregation Inhibitors; C058848:BW A868C; D009599:Nitroprusside; D016718:Arachidonic Acid; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D015232:Dinoprostone; D000109:Acetylcholine; D015230:Prostaglandin D2; D001920:Bradykinin; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin