Influence of adrenomedullin on tone of isolated bovine retinal arteries.
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.
Boussery
Koen
K
Department of Physiology and Pathophysiology, Ghent University, Ghent, Belgium.
Delaey
Christophe
C
Van de Voorde
Johan
J
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*
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