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Prevention by insulin treatment of endothelial dysfunction but not enhanced noradrenaline‐induced contractility in mesenteric resistance arteries from streptozotocin‐induced diabetic rats
Author(s) -
Taylor Paul D.,
Oon Beryl B.,
Thomas Chris R.,
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.tb14020.x
Subject(s) - medicine , endocrinology , mesenteric arteries , myograph , streptozotocin , diabetes mellitus , insulin , sodium nitroprusside , insulin resistance , nitric oxide , artery
1 Streptozotocin‐induced diabetic rats (Wistar) were implanted with sustained release insulin pellets (release rate = 4 u day −1 ) or with placebo pellets (palmitic acid) from the onset of glycosuria. 2 Noradrenaline sensitivity, endothelium‐dependent relaxation to acetylcholine and endothelium‐independent relaxation to sodium nitroprusside were assessed in mesenteric resistance arteries from the insulin‐treated (IT) diabetic animals and compared to placebo‐implanted (PI) diabetics and age‐matched controls. 3 Arteries from PI‐diabetic rats (8–10 weeks) demonstrated an enhanced maximal response to noradrenaline compared to controls, which was not prevented by insulin treatment (control 2.65 ± 0.17 mN mm −1 , n = 18 arteries versus PI‐diabetic 3.73 ± 0.40 mN mm −1 , n = 5, P < 0.05; control versus IT‐diabetic 4.02 ± 0.19 mN mm −1 , n = 22, P < 0.001). Sensitivity to noradrenaline was similar between the three groups. 4 In the presence of the nitric oxide synthase inhibitor N G ‐nitro‐ l ‐arginine methyl ester ( l ‐NAME), IT and PI arteries were more sensitive to noradrenaline than control arteries (pEC 50 : control 5.75 ± 0.08, n = 17, versus PI‐diabetic 6.14 ± 0.09, n = 8, P < 0.05; control versus IT‐diabetic 6.38 ± 0.08, n = 20, P < 0.001). 5 The maximum contractile response to depolarizing 125 mM K + was significantly enhanced in IT‐diabetic arteries but not PI‐diabetic when compared to control arteries (maximum response: control 3.74 ± 0.15 mN mm −1 , n = 18, versus PI‐diabetic 3.61 ± 0.19 mN mm −1 , n = 11, NS; control versus IT‐diabetic 4.66 ± 0.18 mN mm −1 , n = 22, P < 0.001). 6 Endothelium‐dependent relaxation to acetylcholine was profoundly impaired in the PI‐diabetic arteries, but in the IT‐diabetic arteries was not significantly different from controls (pEC 50 : control 7.64 ± 0.19, n = 17, versus PI‐diabetic 6.07 ± 0.12, n = 8, P < 0.001; control versus IT‐diabetic 7.36 ± 0.09, n = 22, NS). 7 Endothelium‐independent relaxation to sodium nitroprusside was slightly but significantly impaired in the PI‐diabetic arteries, but was not significantly different in the IT‐diabetic arteries compared to controls (pEC 50 : control 7.78 ± 0.10, n = 13, versus PI‐diabetic 7.31 ± 0.13, n = 13, P < 0.05; control, versus IT‐diabetic 7.64 ± 0.09, n = 16, NS).