Effects of ischemia‐reperfusion on goat cerebrovascular response to ADP

Abstract

Brain ischemia-reperfusion (I-R) may produce cerebrovascular endothelial dysfunction, and ADP produces endothelial-dependent cerebral vasodilatation. To analyze the effects of I-R on the cerebrovascular response to ADP, 60 min occlusion followed by 60 min reperfusion of the left middle cerebral artery (MCA) was performed in anesthetized goats. Left MCA flow was electromagnetically measured, and resting cerebrovascular resistance after I-R was decreased by 20 % (P<0.01). In control conditions, local, intraarterial injections of ADP (0.03–0.3 μg) and sodium nitroprusside (SNP, 0.3–3 μg) decreased cerebrovascular resistance, and after I-R ADP increased this resistance whereas the effects of SNP were not altered. Then, the animals were killed and 3 mm-long rings from branches of the left (I-R) and right (control) MCA were prepared for isometric tension recording. Arterial segments precontrated with U46619 (3x 10−7 – 10−6 M) showed concentration-dependent relaxations to ADP (10−8–10−5 M) and SNP (10−8–10−4 M), and the relaxations to ADP but not to SNP were lower in I-R arteries. The relaxations to ADP but not to SNP were inhibited by L-NAME (10−4 M) only in control arteries, and the effects of ADP were inhibited by charybdotoxin (10−7 M) plus apamine (10−6 M) only in control arteries. Therefore, I-R may produce cerebral vasodilatation with decreased vasodilator reserve and inversion of the cerebrovascular effects of ADP. This altered effects of ADP may be related to endothelial dysfunction with decreased availability of NO and function of KCa channels. (This work was supported, in part, by CM (GR/SAL/0106/2004) and FMMM)