ASYMMETRICAL RESPONSE OF THE INTRALUMINAL AND EXTRALUMINAL SURFACES OF THE PORCINE RETINAL ARTERY TO EXOGENOUS ADENOSINE

The relative effects of exogenous adenosine applied intraluminally or extraluminally were compared on first-order pig retinal arteries in an isolated perfused artery preparation. First-order retinal arteries wi th at least one side branch were cannulated and perfused at a constant flow in an environmentally-controlled organ bath on the stage of an i nverted microscope. Vessels were precontracted with 10(-4) methoxamine applied extraluminally, which produced a sustained contraction. Then, either extraluminal or intraluminal adenosine was added in increasing concentrations from 10(-9) to 10(-3) M. During these procedures conti nuous measurements of external vessel diameter were made. The average external diameter of the retinal arterial segments used was 127.6 +/- 2.3 mu m (n = 13). Extraluminal methoxamine (10(-4) M) constricted the vessels to 77.9 +/- 2.0% (n = 9) and 78.8 +/- 0.8% (n = 4) of the con trol value for the vessels later exposed to extraluminal and intralumi nal adenosine respectively. Extraluminal adenosine caused a dose-depen dent dilatation which commenced between 10(-7) M and 10(-6) M, and rea ched a percentage dilatation of 22.6 +/- 1.8% (n = 9) at 10(-3) M. For concentrations of 10(-4) M and above, spontaneous oscillations in dia meter were observed for extraluminally-applied adenosine with an avera ge period of 0.46 +/- 0.02 (n = 9) cycles per minute. The average perc entage diameter oscillation was +/- 7.1% of the mean diameter. In cont rast, intraluminal adenosine failed to cause dilatation or spontaneous oscillations at all concentration values, although the dilatory abili ty of these vessels was confirmed by intraluminal application of the C a2+ channel blocker verapamil. In conclusion this study has demonstrat ed that the two sides of the retinal artery wall are differentially se nsitive to adenosine, with the intraluminal route being ineffective. I n vivo, in hypoxic or ischemic situations, adenosine is released by ex traluminal neural tissue and minimizes tissue damage, partially by act ing as a signaller of metabolic status to the vasculature leading to v asodilatation and hence increased local blood flow. This study shows t hat delivery of adenosine for therapeutic purposes through an intralum inal route is not a feasible proposition. This isolated, perfused arte ry technique has considerable potential to improve our understanding o f uptake mechanisms, metabolism and vasoactivity of the retinal vessel wall. (C) 1996 Academic Press Limited