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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

1994; Wiley; Volume: 111; Issue: 1 Linguagem: Inglês

10.1111/j.1476-5381.1994.tb14020.x

1476-5381

Paul Taylor, Beryl B. Oon, Chris R. Thomas, Lucilla Poston,

Cardiovascular Function and Risk Factors

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 NG-nitro-l-arginine methyl ester (l-NAME), IT and PI arteries were more sensitive to noradrenaline than control arteries (pEC50: 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 (pEC50: 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 (pEC50: 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).