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The effect of hyperglycaemia on function of rat isolated mesenteric resistance artery
Author(s) -
Taylor Paul D.,
Poston Lucilla
Publication year - 1994
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1994.tb17064.x
Subject(s) - medicine , endocrinology , acetylcholine , mesenteric arteries , sodium nitroprusside , chemistry , vasodilation , nitric oxide , artery
1 Noradrenaline sensitivity and acetylcholine‐induced relaxation were investigated in mesenteric resistance arteries from female Wistar rats (220–250 g) following exposure to isotonic supraphysiological glucose solutions (20 and 45 m m , in physiological buffer, 2h incubation). 2 Arteries incubated in 20 m m glucose demonstrated enhanced noradrenaline sensitivity compared with those in physiological buffer. 3 Profoundly impaired endothelium‐dependent relaxation to acetylcholine was observed in arteries incubated in 20 and 45 m m glucose. 4 Indomethacin (10 μ m ) normalized noradrenaline sensitivity in 20 m m glucose, but unmasked an enhanced maximum response in 20 and 45 m m glucose relative to controls. 5 Addition of L‐arginine (0.1 μ m ) prevented the abnormality of acetylcholine‐induced relaxation in the 20 m m glucose medium and significantly improved relaxation in 45 m m glucose. 6 The aldose reductase inhibitor, ponalrestat (10 −5 m , ZENECA Pharmaceuticals), prevented impaired acetylcholine‐mediated relaxation in 20 m m glucose and significantly improved relaxation in 45 m m glucose. 7 Indomethacin (10 μ m ) improved maximum relaxation but did not alter impaired sensitivity to acetylcholine in the high glucose media (20 and 45 μ m ). 8 Superoxide dismutase (SOD, 150 u ml −1 ) also prevented impaired acetylcholine‐induced relaxation in 20 m m glucose but not in 45 m m glucose. 9 Endothelium‐independent relaxation to sodium nitroprusside (SNP, 10 −9 ‐10 −5 mM) was normal in 20 m m glucose but was slightly, although significantly impaired by 45 m m glucose. 10 Enhanced responsiveness of rat isolated mesenteric resistance arteries to noradrenaline caused by elevated glucose would appear to be mediated through abnormal cyclo‐oxygenase activity and the reduced tonic release of nitric oxide. 11 Hyperglycaemia may lead to abnormal endothelium‐dependent relaxation in these arteries through several mechanisms which include a role for increased free radical production, polyol pathway activation and altered L‐arginine metabolism.