Abstract no.: 1 The vasorelaxing influence of adrenomedullin in isolated bovine retinal arteries.

摘要

Aims: Adrenomedullin (AM), a peptide noted in a broad variety of tissues and cells, is known to induce relaxations in different vascular beds and isolated blood vessels, including the (extra-ocular) central retinal artery. A role for AM in the regulation of ocular blood flow has been suggested, but so far no data were available on the direct influence of AM on smooth muscle tone in intra-ocular retinal arteries. The present study therefore aimed to assess and to characterise the vasorelaxing effect of AM on isolated (intra-ocular) bovine retinal arteries (BRA). Methods: Retinal arteries were isolated from bovine eyes and mounted in a wire-myograph for isometric tension recording. Concentration-response curves were constructed by cumulative addition of AM (1 pM to 0.1 muM) in the organ bath. Results: AM caused a concentration-dependent relaxation of the BRA. The AM-response was reduced after removal of the endothelium of the BRA (30 nM: from 38.14 +/- 4.90% to 25.71 +/- 4.32% relaxation, n = 7, P < 0.05). Also treatment of the BRA with the NOS-inhibitor L-NA or the soluble guanylyl cyclase inhibitor ODQ significantly reduced the AM-response, whereas cyclo-oxygenase inhibition or the adenosine receptor antagonist 8-SPT had no effect. The AM-receptor antagonist AM 22-52 caused a small, but significant reduction in the AM-response (30 nM: from 55.33 +/- 9.65% to 47.50 +/- 8.26% relaxation, n = 6, P < 0.05). The CGRP-receptor antagonist CGRP 8-37 caused a more pronounced decrease in AM-response (30 nM: from 55.43 +/- 10.53% to 17.77 +/- 6.57% relaxation, n = 6, P < 0.05). Conclusion: The present study demonstrates that AM induces vasodilation in isolated BRA. Thereby, our findings support the hypothesis that AM may have a role in the regulation of retinal blood flow. 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.