Etanercept, a tumor‐necrosis factor (TNF‐α) inhibitor, improves endothelial function of contralateral middle cerebral artery after cerebral ischemia in hypertensive rats

Abstract

Middle cerebral artery (MCA) occlusion (MCAO) causes endothelial dysfunction in the ischemic MCA (Marrelli et al., AJP 276:H33‐H41), and in small mesenteric arteries (Martinez‐Revelles et al., JPET 325: 363–9). The effect of MCAO on the contralateral MCA (CL MCA) however is unknown. In hypertensive rats MCA remodeling impairs artery function, and etanercept (ETN) attenuates this. We hypothesized that CL MCA dilation is impaired after MCAO and that ETN will improve this. 12 week old stroke prone spontaneously hypertensive rats, ETN‐treated from 6 weeks of age (ETN IR) or untreated (IR), underwent 1 hour of MCAO and 47 hours reperfusion. SHAM controls were generated. Cerebral blood flow (CBF) was measured by laser Doppler flowmetry. CL MCAs were mounted in a pressure myograph under physiological conditions. Endothelial function was assessed by intraluminal perfusion of ADP. Data are presented as mean ± SEM. Tone generation was not different between the groups. ADP mediated dilation was impaired in the IR group and this was ameliorated by ETN treatment (p<0.05). This caused a small, but insignificant (p=0.12), increase in post‐MCAO CBF in the ETN IR group. Our data suggest that ETN improves CL MCA endothelial function and may improve post‐MCAO CBF in hypertensive rats. (AHA0840122N) SHAM (n=2) ETN IR (n=3) IR (n=4) Tone (%) 32.6±5.4 33.2±7.1 36.9±4.7 Maximum increase in lumen diameter with ADP (μm) 62.5±12.5 60.6±7.5 28.2±7.8 Flow (% of pre‐MCAO) 94.5±10.9 86.6±7.0 62.6±10.1