Attenuation of ischemia-induced extracellular adenosine accumulation by homocysteine.
The purpose of this study was to determine the effects of homocysteine, which consumes intracellular adenosine via formation of S-adenosylhomocysteine, on interstitial fluid (ISF) adenosine and cerebral blood flow (CBF) before, during, and after cerebral ischemia. Microdialysis probes, used to measure local CBF (H2 clearance) and to sample ISF, were implanted bilaterally into the caudate nucleus of halothane-anesthetized rats (n = 8). L-Homocysteine thiolactone was administered locally via one of the probes. Animals were exposed to 20 min of ischemia, induced by bilateral carotid occlusion plus hemorrhage to an arterial blood pressure of 50 mm Hg, followed by 60 min of reperfusion. Before ischemia, CBF and dialysate adenosine were decreased with homocysteine. During ischemia and early reperfusion, dialysate purine metabolites increased on both sides of the brain; however, the ischemia-induced increase in adenosine was attenuated on the side of local homocysteine. CBF was lower on the side of homocysteine throughout reperfusion. These data demonstrate that homocysteine (a) decreases basal ISF adenosine and CBF, (b) attenuates the increase in dialysate adenosine during ischemia, and (c) reduces hyperemia during early reperfusion.
Sciotti
V M
VM
Department of Pathology, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14215.
Van Wylen
D G
DG
D000241:Adenosine / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism*; D002545:Brain Ischemia / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000378:metabolism; D006710:Homocysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000378:metabolism; D007288:Inosine / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012435:S-Adenosylhomocysteine / Q000378:metabolism
D007042:Hypoxanthines; D006710:Homocysteine; D019271:Hypoxanthine; D007288:Inosine; D012435:S-Adenosylhomocysteine; C007957:homocysteine thiolactone; D000241:Adenosine