Exogenous endothelin-1 improves microvascular oxygen balance during focal cerebral ischemia in the rat

We tested the hypothesis that endothelin-1 (ET-1), a cerebrovasoconstrictive peptide, would alter microvascular oxygen balance during focal cerebral ischemia. In this study, male Wistar rats were placed in control (n=9) and ET-1-treated (n=9) groups. Cortical ischemia was induced by middle cerebral artery (MCA) occlusion in isoflurane (1.4%) anesthetized rats. Forty minutes after MCA occlusion, 10(-7) M ET-1 or saline was applied to the ischemic cortex (IC) for a period of 20 min; the fluid was changed every 5 min. After 1 h of ischemia, regional cerebral blood flow (rCBF) was determined using a 14C-iodoantipyrine autoradiographic technique. Regional arterial and venous oxygen saturation were determined microspectrophotometrically. The cerebral blood flow (45% control, 45% ET-l) and oxygen consumption (24% control, 44% ET-1) of the IC were significantly lower than the contralateral cortex. ET-1 of 10(-7) M did not cause a statistically significant alteration in regional cerebral blood flow or oxygen consumption of the IC, but did increase the average venous O(2) saturation of the IC from 50 +/- 1% to 55 +/- 2% (p<0.04). A significant (p<0.05) increase was observed in O(2) supply/consumption ratio in the ET-1-treated IC (2.79 +/- 0.26 ml O(2)/min/100 g in ET-1-treated IC vs. 2.41 +/- 0.12 ml O(2)/min/100 g in the control IC) compared to the control IC. ET-1 also significantly lowered the frequency of small veins with less than 50% O(2) saturation in the IC (39 out of 70 veins in IC vs. 17 out of 70 veins in ET-1-treated IC). Thus, the exogenous application of 10(-7) M ET-1 improved microvascular oxygen supply/consumption balance during focal cerebral ischemia.