HIGH GLUCOSE-CONCENTRATIONS DILATE CEREBRAL-ARTERIES AND DIMINISH MYOGENIC TONE THROUGH AN ENDOTHELIAL MECHANISM

Background and Purpose Diabetes is associated with cerebrovascular dis ease and impaired autoregulation of cerebral blood flow. The purpose o f this study was to determine the effect of acute glucose exposure on basal tone and myogenic reactivity of isolated rat cerebral arteries. Methods Posterior cerebral arteries (PCAs, n=38) were dissected from m ale Wistar rats and mounted on glass cannulas in a system that allowed control of transmural pressure (TMP) and measurement of lumen diamete r. Arteries were exposed to various concentrations of glucose, and the amount of basal tone and reactivity to TMP was measured. The effect o f elevated glucose on cerebral endothelial modulation of basal tone wa s determined by mechanical denudation and the use of inhibitors of bot h nitric oxide and prostaglandin synthesis. Results Arteries exposed t o 44 versus 5.5 mmol/L glucose developed significantly less intrinsic tone (percent tone, 2+/-1% versus 28+/-2%; P<.01) and responded passiv ely to increases in TMP. Preexisting tone present in 5.5 mmol/L glucos e was eliminated on exposure to 44 mmol/L glucose, which decreased ton e from 30+/-5% to 5+/-4% (P<.01). Glucose-induced dilations were conce ntration dependent such that half-maximal responses were obtained at 2 5+/-2 mmol/L. Endothelial removal abolished this effect, and the amoun t of tone was similar in 5.5 versus 44 mmol/L glucose (percent tone, 4 6+/-6% versus 49+/-5%; P>.05), as did inhibition of nitric oxide produ ction with 0.3 mmol/L nitro-L-arginine (percent tone, 52+/-4% versus 4 6+/-3%; P>.05); however, blockade of the cyclooxygenase pathway with i ndomethacin (10(-5) mmol/L) only partially inhibited the dilation to g lucose (percent tone, 32+/-3% in 5.5 mmol/L versus 12.4+/-3% in 44 mmo l/L; P<.01). Conclusions Acute glucose exposure dilates arteries with intrinsic tone and impairs cerebrovascular reactivity to TMP via an en dothelium-mediated mechanism that involves nitric oxide and prostaglan dins.