Effect of betaxolol, timolol and nimodipine on human and pig retinal arterioles.
This study tested the hypothesis that the beta-adrenergic antagonists betaxolol and timolol, cause retinal arteriolar vasodilatation in addition to their ability to reduce intraocular pressure (IOP), and compared their vasodilatory ability with that of a known Ca2+ channel entry blocker nimodipine in donor human and pig isolated perfused retinal arterioles. This study was performed using a microperfusion technique specifically established to allow investigations in arterioles as small as the first order human and pig retinal arterioles (approximately 100 microns diameter). The scarcity of viable human tissue was overcome by the successful development of controlled rate freezing and cryopreservation techniques which were able to preserve the vascular responsiveness of the retinal arterioles, thus enabling multiple experiments to be performed on segments of retinal arterioles from each individual donor eye. Furthermore, relaxation by acetylcholine in noradrenaline contracted pig retinal arterioles showed that endothelial cell function was well maintained after cryopreservation (n = 8). Baseline diameters of retinal arterioles used in the main studies were: cryopreserved human 92.3 +/- 3.4 microns (n = 44), fresh pig 94.7 +/- 2.2 microns (n = 42), and cryopreserved pig 94.3 +/- 2.3 microns (n = 30). Precontraction with extraluminal endothelin-1 (ET-1) 10(-9) M reduced the diameters to 74.3 +/- 0.9%, 71.6 +/- 1.6% and 72.5 +/- 0.9% respectively. Intraluminally applied nimodipine and betaxolol caused a significant dose dependent dilatation (P < 0.001) in human retinal arterioles with a threshold of 10(-12) M. Timolol did not produce a significant dilatation in human arterioles. Timolol produced a small but significant dilatation in fresh and cryopreserved pig arterioles but the dilatation with betaxolol and nimodipine was significantly larger. The nimodipine and betaxolol dose response curves were not significantly different in human arterioles, but nimodipine produced significantly greater dilatation than betaxolol (P < 0.001) in fresh and cryopreserved pig arterioles. Both nimodipine and betaxolol were significantly more effective vasodilators than timolol (P < 0.001) in human and pig retinal arterioles.
Yu
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Lions Eye Institute and Centre for Ophthalmology and Visual Science, University of Western Australia, Nedlands, Australia.
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Cringle
S J
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Alder
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VA
Yu
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Desantis
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D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000368:Aged; D000818:Animals; D001160:Arterioles / Q000187:drug effects; D015784:Betaxolol / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015925:Cryopreservation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D008875:Middle Aged; D009553:Nimodipine / Q000494:pharmacology; D012161:Retinal Artery / Q000187:drug effects*; D013552:Swine; D013999:Timolol / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
D000319:Adrenergic beta-Antagonists; D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D009553:Nimodipine; D013999:Timolol; D015784:Betaxolol