Acute hyperglycemia depresses arteriolar NO formation in skeletal muscle.

In the rat intestinal and cerebral microvasculatures, acute d-glucose hyperglycemia suppresses endothelium-dependent dilation to ACh without affecting endothelium-independent dilation to nitroprusside. This study determined whether acute hyperglycemia suppressed arteriolar wall nitric oxide concentration ([NO]) at rest or during ACh stimulation and inhibited nitroprusside-, ACh- or contraction-induced dilation of rat spinotrapezius arterioles. Vascular responses were measured before and after 1 h of topical 300 mg/100 mld-glucose; arteriolar [NO] was measured with NO-sensitive microelectrodes. Arteriolar dilation to ACh was not significantly altered after superfusion of 300 mg/100 mld-glucose. However, after hyperglycemia, arteriolar [NO] was not increased by ACh, compared with a 300 nM increase attained during normoglycemia. Arteriolar dilation to submaximal nitroprusside and muscle contractions was enhanced by hyperglycemia. These results indicated that in the rat spinotrapezius muscle, acute hyperglycemia suppressed arteriolar NO production while simultaneously augmenting vascular smooth muscle responsiveness to nitroprusside, presumably through cGMP-mediated mechanisms. In effect, this may have allowed ACh- and muscle contraction-induced vasodilation to be maintained during hyperglycemia despite an impaired NO system.