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Functional and Molecular Characterization of the Endothelin System in Retinal Arterioles

¹From the Departments of Ophthalmology and ²Surgery, Scott and White Eye Institute, Temple, Texas; the ³Department of Systems Biology and Translational Medicine, College of Medicine, Texas A&M Health Science Center, Temple, Texas; and the ⁴Department of Ophthalmology, Asahikawa Medical College, Asahikawa, Japan.

PURPOSE. Activation of the endothelin (ET) system has been implicated in the pathogenesis of retinal ischemic disease. Although ET-1, the predominant endogenous isoform of ET, has been shown to cause constriction of retinal vessels, the expression and functional significance of its synthesis and the involved specific ET receptors in retinal arterioles remain unknown. The authors examined the roles of ET_A and ET_B receptors and of endothelin-converting enzyme (ECE)-1 in ET-1–induced vasomotor responses of single retinal arterioles.

METHODS. To exclude systemic confounding effects, porcine retinal arterioles were isolated for vasoreactivity and molecular studies.

RESULTS. Isolated and pressurized retinal arterioles developed basal tone and constricted in a manner dependent on concentration to ET-1. ET-1 precursor big ET-1 elicited time-dependent vasoconstriction over 20 minutes, which was blocked by the ECE-1 inhibitor phosphoramidon. ET_A receptor antagonist BQ123 inhibited most (approximately 90%) of vasoconstrictions to ET-1 and big ET-1. ET_B receptor agonist sarafotoxin also elicited concentration-dependent constriction of retinal arterioles but with significantly less potency than ET-1. ET_B receptor antagonist BQ788 abolished vasoconstriction to sarafotoxin but only slightly reduced responses to ET-1 and big ET-1. Protein and mRNA expressions of ET_A, ET_B, and ECE-1 were detected in retinal arterioles. Immunohistochemistry revealed ET_A and ET_B receptors predominantly in smooth muscle and ECE-1 predominantly in endothelium and smooth muscle.

CONCLUSIONS. ET-1 elicits constriction of retinal arterioles predominantly through the activation of smooth muscle ET_A receptors. Endogenous production of ET-1 from vascular ECE-1 is sufficient to evoke ET_A receptor–dependent constriction in retinal arterioles.

This article has been cited by other articles:

				T. W. Hein, R. H. Rosa Jr, Z. Yuan, E. Roberts, and L. Kuo Divergent Roles of Nitric Oxide and Rho Kinase in Vasomotor Regulation of Human Retinal Arterioles Invest. Ophthalmol. Vis. Sci., March 1, 2010; 51(3): 1583 - 1590. [Abstract] [Full Text] [PDF]