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

Abstract

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.