Hypoxia reduces cerebrovascular myogenic reactivity in diabetes

Abstract

Diabetes increases the risk for acute ischemic stroke and poor stroke outcome. The outcome of cerebral ischemia is mainly determined by vessel diameter which is regulated by myogenic, endothelial, and neuronal factors. However, how diabetes affects myogenic reactivity and tone of cerebral vessels, especially under hypoxic conditions, is not known. We hypothesized that myogenic tone is increased in diabetes and that ischemia reduces cerebrovascular myogenic reactivity, thereby making the affected brain more prone to edema and bleeding. Lumen diameter (LD) and wall thickness (WT) of middle cerebral arteries (MCAs) from Wistar (n=6–8) and type 2 diabetic Goto‐Kakizaki (GK) rats (n=6–8) were analyzed under normoxic and hypoxic conditions and myogenic tone was calculated. In vitro hypoxia was achieved by exposing the isolated vessels to 95% N2/5%CO2 in 1 mM glucose to mimic oxygen‐glucose deprivation. The autoregulatory capacity of vessels in all groups was retained across the normal range. Under normoxic conditions, active LD was smaller in diabetes and myogenic tone was higher across the pressure range. Ischemia reduced myogenic tone in both groups but this effect was more significant in diabetic animals, potentially making them more likely to bleed after ischemia‐reperfusion injury. Hypoxia increased WT in Wistars alone, possibly making them less likely to hemorrhage and more prone to larger cerebral infarct.