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T.W. Hein, Z. Yuan, W. Xu, M.I. Pechal, T. Nagaoka, A. Yoshida, L. Kuo; Functional and Molecular Characterization of the Endothelin System in Retinal Arterioles . Invest. Ophthalmol. Vis. Sci. 2006;47(13):1791.
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© ARVO (1962-2015); The Authors (2016-present)
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 large retinal arteries, the expression and functional significance of specific ET receptors in retinal microvessels remain unknown. We examined the roles of ETA and ETB receptors, as well as endothelin converting enzyme (ECE), in ET–1–induced constriction of retinal arterioles in vitro.
Second–order porcine retinal arterioles were isolated, cannulated, and pressurized (55 cmH2O) without flow. Videomicroscopic techniques were employed to record diameter changes in response to ET agonists. ET production was measured using an ET ELISA. RT/PCR was performed for detection of ETA, ETB, and ECE mRNA.
All vessels developed basal tone (∼70 µm i.d.) and constricted dose–dependently to ET–1 (10 pM to 1 µM), ETB receptor agonist sarafotoxin (10 pM to 1 µM), and ET–1 precursor big ET–1 (10 nM to 0.1 µM). Vasoconstriction to ET–1 and sarafotoxin commenced within 1 min whereas the response to big ET–1 initiated about 5 min after drug administration. Vasoconstriction to ET–1 was more potent than that to sarafotoxin. ETB receptor blocker BQ788 abolished vasoconstriction to sarafotoxin, but only slightly reduced (∼10%) the response to ET–1. In contrast, ETA receptor blocker BQ123 inhibited a majority (∼80%) of ET–1–induced vasoconstriction. Vasoconstriction elicited by big ET–1 was inhibited by ECE antagonist phosphoramidon and by BQ123. ET production from big ET–1 was 3–fold higher in retinal arterioles than in neural retina tissue. Expression of ETA, ETB, and ECE mRNA was also consistently greater in retinal arterioles.
These data suggest that the ET system is expressed in retinal arterioles. Endogenous production of ET–1 from ECE is capable of evoking constriction of retinal arterioles primarily via ETA receptor activation. A better understanding of the ET system in the retinal circulation could lead to new therapeutic modalities for retinal vascular diseases elicited by ET–1.
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