Acute hyperglycemia depresses arteriolar NO formation in skeletal muscle

In the rat intestinal and cerebral microvasculatures, acute D-glucose hyper glycemia suppresses endothelium-dependent dilation to ACh without affecting endothelium-independent dilation to nitroprusside. This study determined w hether acute hyperglycemia suppressed arteriolar wall nitric oxide concentr ation ([NO]) at rest or during ACh stimulation and inhibited nitroprusside- , ACh- or contraction-induced dilation of rat spinotrapezius arterioles. Va scular responses were measured before and after 1 h of topical 300 mg/100 m i D-glucose; arteriolar [NO] was measured with NO-sensitive microelectrodes . Arteriolar dilation to ACh was not significantly altered after superfusio n of 300 mg/100 mi D-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 c ontractions 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 responsi veness to nitroprusside, presumably through cGMP-mediated mechanisms. In ef fect, this may have allowed ACh- and muscle contraction-induced vasodilatio n to be maintained during hyperglycemia despite an impaired NO system.