June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Acute and Chronic Hyperglycemia Enhance Constriction of Retinal Venules to Endothelin-1
Author Affiliations & Notes
  • Yen-Lin Chen
    Departments of Medical Physiology and Surgery, Texas A&M University Health Science Center, Temple, Texas, United States
  • Wenjuan Xu
    Departments of Medical Physiology and Surgery, Texas A&M University Health Science Center, Temple, Texas, United States
    Department of Ophthalmology, Baylor Scott & White Health, Temple, Texas, United States
  • Lih Kuo
    Departments of Medical Physiology and Surgery, Texas A&M University Health Science Center, Temple, Texas, United States
    Department of Ophthalmology, Baylor Scott & White Health, Temple, Texas, United States
  • Travis W. Hein
    Departments of Medical Physiology and Surgery, Texas A&M University Health Science Center, Temple, Texas, United States
    Department of Ophthalmology, Baylor Scott & White Health, Temple, Texas, United States
  • Footnotes
    Commercial Relationships   Yen-Lin Chen, None; Wenjuan Xu, None; Lih Kuo, None; Travis W. Hein, None
  • Footnotes
    Support  NIH Grants R01EY023335 and R01EY024624, Kruse Chair Endowment Fund, and Retina Research Foundation
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 5800. doi:
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      Yen-Lin Chen, Wenjuan Xu, Lih Kuo, Travis W. Hein; Acute and Chronic Hyperglycemia Enhance Constriction of Retinal Venules to Endothelin-1. Invest. Ophthalmol. Vis. Sci. 2017;58(8):5800.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Hyperglycemia, a hallmark of diabetes, is associated with increased retinal fluid filtration, a process heavily influenced by the postcapillary pressure and venous constriction. Although the ocular level of vasoconstrictor endothelin-1 (ET-1) is elevated in hyperglycemia/diabetes, its impact and mechanistic action on venular vasomotor activity in the retina remain unclear. Herein, we characterized the constriction of retinal venules to ET-1 and determined the relative roles of ET-1 receptor subtypes and L-type voltage-operated calcium channels (L-VOCCs) in this vasomotor regulation with and without hyperglycemic insults.

Methods : Retinal venules (<150 µm maximum diameter) were isolated from streptozocin-induced diabetic pigs (2-wk; chronic hyperglycemia: 286 ± 67 mg/dl) or age-matched control pigs (euglycemia: 71 ± 5 mg/dl) and then cannulated and pressurized to 5 cmH2O for vasoreactivity study. For acute hyperglycemia study, vessels from nondiabetic pigs were exposed intraluminally to high glucose (25 mM ≈ 450 mg/dl) for 2 hr, and normal glucose (5 mM ≈ 90 mg/dl) served as the control.

Results : Retinal venules developed basal tone (constricted to about 90% of maximum diameter), which was not influenced by the glucose level. ET-1 elicited concentration-dependent vasoconstriction that was significantly increased in a similar manner after exposure to acute or chronic hyperglycemia. By contrast, vasoconstriction to L-VOCC agonist Bay K8644 was slightly reduced by hyperglycemia. The L-VOCC inhibitor nifedipine abolished basal tone and vasoconstriction to Bay K8644 but did not alter ET-1-induced vasoconstriction. Vasoconstriction to ET-1 was prevented in the presence of the ETA receptor antagonist BQ123 but not the ETB receptor antagonist BQ788 during normal glucose exposure. However, treatment with either BQ123 or BQ788 diminished ET-1-induced vasoconstriction after hyperglycemia.

Conclusions : Retinal venules develop L-VOCC-dependent basal tone but constrict in an L-VOCC-independent manner to ET-1. In the presence of normal glucose, ET-1 elicits ETA receptor-dependent vasoconstriction. Hyperglycemia appears to enhance ET-1-induced vasoconstriction via activation of both ETA and ETB receptors. The ability of hyperglycemia to augment venular constriction to ET-1 might elevate postcapillary pressure and promote retinal tissue edema during diabetic retinopathy.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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