title: The vasodilatory effect of juxta-arteriolar microinjection of endothelinA receptor inhibitor in healthy and acute branch retinal vein occlusion minipig retinas.
abstract: Purpose. To investigate the effect of the endothelin(A) receptor inhibitor BQ-123 on the retinal arteriolar vasculature in minipig retinas in normal eyes and eyes with acute branch retinal vein occlusion (BRVO). Methods. Seven healthy eyes of seven minipigs and six eyes of six minipigs with experimental BRVO were evaluated under systemic anesthesia. An intravitreal juxta-arteriolar microinjection of 30 microL BQ-123 0.61 microg/mL (pH 7.4) was performed in all but one eye from each group, into which the physiologic saline vehicle alone was injected. Vessel-diameter changes were measured with a retinal vessel analyzer. Results. In healthy minipig retinas (n = 6), arteriolar diameter (+/-SD) increased 6.19% +/- 3.55% (P < 0.05), 25.98% +/- 2.37% (P < 0.001), 23.65% +/- 1.2% (P < 0.001), and 16.84% +/- 1.95% (P < 0.001), at 1, 5, 10, and 15 minutes, respectively, after BQ-123 microinjection. Two hours after experimental BRVO (n = 5), the retinal arteriolar diameter had decreased (13.07% +/- 5.7%; P < 0.01). One, 5, 10, and 15 minutes after BQ-123 microinjection, retinal arteriolar diameter had increased by 7.14% +/- 3.3% (P < 0.01), 26.74% +/- 7.63% (P < 0.001), 23.67% +/- 6.4% (P < 0.001), and 16.09% +/- 3.41% (P < 0.001), respectively. Vehicle only injection had no vasoactive effect on physiologic or BRVO retinas. Conclusions. A significant increase in retinal arteriolar diameter was demonstrated after juxta-arteriolar BQ-123 microinjection in healthy and in acute BRVO minipig retinas. The results suggest a role for endothelin-1 in maintaining retinal basal arteriolar tone. Reversing the BRVO-related vasoconstriction by juxta-arteriolar BQ-123 microinjection could bring a new perspective to the management of BRVO.
authors.affiliation: Laboratory of Neurobiology and Retinal Vascular Physiology, Ophthalmology Service, Department of Clinical Neurosciences, Geneva School of Medicine, Geneva, Switzerland.
authors.forename: Alexandros N
authors.initials: AN
authors.lastname: Stangos
authors.forename: Ioannis K
authors.initials: IK
authors.lastname: Petropoulos
authors.forename: Jean-Antoine C
authors.initials: JA
authors.lastname: Pournaras
authors.forename: Efstratios
authors.initials: E
authors.lastname: Mendrinos
authors.forename: Constantin J
authors.initials: CJ
authors.lastname: Pournaras
mesh_terms: D000208:Acute Disease; D000818:Animals; D001160:Arterioles / Q000502:physiology; D004195:Disease Models, Animal; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology; D008845:Microinjections; D009131:Muscle, Smooth, Vascular / Q000502:physiology; D010456:Peptides, Cyclic / Q000008:administration & dosage*; D012161:Retinal Artery / Q000502:physiology*; D012170:Retinal Vein Occlusion / Q000503:physiopathology*; D013552:Swine; D013556:Swine, Miniature; D014664:Vasodilation / Q000502:physiology*
chemical_list: D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; C072247:cyclo(Trp-Asp-Pro-Val-Leu)