High glucose concentrations dilate cerebral arteries and diminish myogenic tone through an endothelial mechanism.
OBJECTIVE
Diabetes is associated with cerebrovascular disease and impaired autoregulation of cerebral blood flow. The purpose of 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 male Wistar rats and mounted on glass cannulas in a system that allowed control of transmural pressure (TMP) and measurement of lumen diameter. Arteries were exposed to various concentrations of glucose, and the amount of basal tone and reactivity to TMP was measured. The effect of elevated glucose on cerebral endothelial modulation of basal tone was determined by mechanical denudation and the use of inhibitors of both nitric oxide and prostaglandin synthesis.


RESULTS
Arteries exposed to 44 versus 5.5 mmol/L glucose developed significantly less intrinsic tone (percent tone, 2 +/- 1% versus 28 +/- 2%; P < .01) and responded passively to increases in TMP. Preexisting tone present in 5.5 mmol/L glucose was eliminated on exposure to 44 mmol/L glucose, which decreased tone from 30 +/- 5% to 5 +/- 4% (P < .01). Glucose-induced dilations were concentration dependent such that half-maximal responses were obtained at 25 +/- 2 mmol/L. Endothelial removal abolished this effect, and the amount of tone was similar in 5.5 versus 44 mmol/L glucose (percent tone, 46 +/- 6% versus 49 +/- 5%; P > .05), as did inhibition of nitric oxide production with 0.3 mmol/L nitro-L-arginine (percent tone, 52 +/- 4% versus 46 +/- 3%; P > .05); however, blockade of the cyclooxygenase pathway with indomethacin (10(-5) mmol/L) only partially inhibited the dilation to glucose (percent tone, 32 +/- 3% in 5.5 mmol/L versus 12.4 +/- 3% in 44 mmol/L; P < .01).


CONCLUSIONS
Acute glucose exposure dilates arteries with intrinsic tone and impairs cerebrovascular reactivity to TMP via an endothelium-mediated mechanism that involves nitric oxide and prostaglandins.
Cipolla
M J
MJ
Department of Surgery, Oregon Health Sciences University, Portland. cipollam@ohsu.edu
Porter
J M
JM
Osol
G
G
D000818:Animals; D001794:Blood Pressure; D002536:Cerebral Arteries / Q000187:drug effects* / Q000473:pathology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D003925:Diabetic Angiopathies / Q000209:etiology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000503:physiopathology*; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D011453:Prostaglandins / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D014665:Vasodilator Agents; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D005947:Glucose; D007213:Indomethacin