N‐methyl‐D‐aspartate (NMDA) increases cortical blood flow in part by evoking cortical spreading depression (CSD) in insulin resistant Zucker rats

Abstract

Insulin resistance (IR) leads to selective impairment of responsiveness of larger cerebral arteries but effects on total cortical blood flow (CoBF) have not been examined. The purpose of our study was to test whether NMDA‐induced cerebral vasodilation is altered in the Zucker obese rat, a genetic model of IR. Anesthetized, ventilated, 12 week old male Zucker obese (n=8) and lean (n=8) rats were equipped with closed cranial windows. NMDA (10‐4, 10‐3 M) was applied to the parietal cortex, while CoBF (Laser‐Doppler flowmetry) and cortical DC potential were monitored. NMDA evoked CSD often at 10‐4 and always at 10‐3 M concentration. The amplitude of the response was similar in the two groups at all doses. After the transient CSD‐induced hyperemia, sustained increases in CoBF occurred with both 10‐4–10‐3 M NMDA at 6–10 minutes and there were no differences between obese and lean rats. Increases in CoBF during application of 10‐4 and 10‐3 M NMDA (% of baseline, 6–10th min of NMDA, *p<0.05 compared to vehicle) were 12±6 and 40±9*% in lean and 19±8% and 40±8*% in obese rats. Thus, similar to mice, the total cerebral vascular response to NMDA is due to direct effects by individual neurons as well as evoked CSDs. The retention of normal increases in CoBF in obese rats to NMDA/CSD indicates microvascular responses to some stimuli are intact in IR animals. Supported by the NIH (HL30260, HL65380, HL77731) and by the OTKA (K68976 and K63401).