title: Influence of adrenomedullin on tone of isolated bovine retinal arteries.
abstract: OBJECTIVE
  To assess and characterize the vasorelaxing effect of adrenomedullin (AM) on isolated bovine retinal arteries (BRAs).
  
  
  METHODS
  Retinal arteries were isolated from bovine eyes and mounted in a wire myograph for isometric tension recording. Concentration-response curves were generated by cumulative addition of AM (1 pM to 0.1 micro M) to the organ bath.
  
  
  RESULTS
  AM caused a concentration-dependent relaxation of the BRAs. Removal of the endothelium of the BRAs, inhibition of nitric oxide synthase with -nitro-L-arginine (L-NA) or inhibition of soluble guanylyl cyclase with 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) significantly reduced the AM response. Cyclooxygenase inhibition with indomethacin or sodium diclofenac did not reduce, but rather increased, vasodilation. The AM-receptor antagonist AM 22-52 slightly, but significantly, reduced the AM response, whereas the CGRP-receptor antagonist CGRP 8-37 caused a more pronounced reduction. The adenosine receptor antagonist 8-(p-sulfophenyl) theophylline (8-SPT) did not affect AM-induced vasorelaxation. Inhibition of several intracellular calcium ([Ca(2+)](i))-reducing mechanisms failed to block the relaxation induced by AM. Only inhibition of the plasma membrane Ca(2+)-adenosine triphosphatase (ATPase) with vanadate significantly attenuated the AM response.
  
  
  CONCLUSIONS
  AM induces vasodilation in isolated bovine retinal arteries. Endothelium-derived NO and stimulation of CGRP- and AM-receptors appear to be involved in the AM response, whereas prostanoids and activation of adenosine receptors are not involved. Activation of Ca(2+)-extrusion by the plasma membrane Ca(2+)-ATPase may elicit the relaxation of BRAs in response to AM.
authors.affiliation: Department of Physiology and Pathophysiology, Ghent University, Ghent, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Boussery
authors.forename: Christophe
authors.initials: C
authors.lastname: Delaey
authors.forename: Johan
authors.initials: J
authors.lastname: Van de Voorde
mesh_terms: D053607:Adrenomedullin; D000818:Animals; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D007537:Isometric Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D009213:Myography; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D010455:Peptides / Q000494:pharmacology*; D011188:Potassium / Q000378:metabolism; D058265:Receptors, Adrenomedullin; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D018000:Receptors, Peptide / Q000037:antagonists & inhibitors / Q000378:metabolism; D012161:Retinal Artery / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D010455:Peptides; D058265:Receptors, Adrenomedullin; D018015:Receptors, Calcitonin Gene-Related Peptide; D018000:Receptors, Peptide; D014665:Vasodilator Agents; D053607:Adrenomedullin; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D006162:Guanylate Cyclase; D011188:Potassium; D002118:Calcium