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 addi tion to their ability to reduce intraocular pressure (IOP), and compar ed their vasodilatory ability with that of a known Ca2+ channel entry blocker nimodipine in donor human and pig isolated perfused retinal ar terioles.This study was performed using a microperfusion technique spe cifically established to allow investigations in arterioles as small a s the first order human and pig retinal arterioles (similar to 100 mu m diameter). The scarcity of viable human tissue was overcome by the s uccessful 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 perf ormed 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 reti nal arterioles used in the nain studies were: cryopreserved human 92.3 +/- 3.4 mu m (n = 44), fresh pig 94.7 +/- 2.2 mu m (n = 42), and cryo peserved pig 94.3 +/- 2.3 mu m (n = 30). Precontraction with extralumi nal endothelin-l (ET-1) 10(-9) reduced the diameters to 7.43 +/- 0.9%, 71.6 +/- 1.6% and 72.5 +/- 0.9% respectively. Intraluminaily applies: nimodipine and betaxolol caused a significant dose dependent dilatati on (P < 0.001) in human retinal arterioles with a threshold of 10(-12) M. Timolol did not produce a significant dilatation in human arteriol es. Timolol produced a small but significant dilatation in fresh and c ryopreserved pig arterioles but the dilatation with betaxolol and nimo dipine was significantly larger. The nimodipine and betaxolol dose res ponse 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 timo lol (P < 0.001) in human and pig retinal arterioles. (C) 1998 Academic Press.