Hyperglycemia Augments Endothelin-1–Induced Constriction of Human Retinal Venules

PURPOSE: Endothelin-1 (ET-1) is a potent vasoactive factor implicated in development of diabetic retinopathy, which is commonly associated with retinal edema and hyperglycemia. Although the vasomotor activity of venules contributes to the regulation of tissue fluid homeostasis, responses of human retinal venules to ET-1 under euglycemia and hyperglycemia remain unknown and the ET-1 receptor subtype corresponding to vasomotor function has not been determined. Herein, we addressed these issues by examining the reactivity of isolated human retinal venules to ET-1, and results from porcine retinal venules were compared. METHODS: Retinal tissues were obtained from patients undergoing enucleation. Human and porcine retinal venules were isolated and pressurized to assess diameter changes in response to ET-1 after exposure to 5 mM control glucose or 25 mM high glucose for 2 hours. RESULTS: Both human and porcine retinal venules exposed to control glucose developed similar basal tone and constricted comparably to ET-1 in a concentration-dependent manner. ET-1–induced constrictions of human and porcine retinal venules were abolished by ET(A) receptor antagonist BQ123. During high glucose exposure, basal tone of human and porcine retinal venules was unaltered but ET-1–induced vasoconstrictions were enhanced. CONCLUSIONS: ET-1 elicits comparable constriction of human and porcine retinal venules by activation of ET(A) receptors. In vitro hyperglycemia augments human and porcine retinal venular responses to ET-1. TRANSLATIONAL RELEVANCE: Similarities in vasoconstriction to ET-1 between human and porcine retinal venules support the latter as an effective model of the human retinal microcirculation to help identify vascular targets for the treatment of retinal complications in patients with diabetes.