Endothelial dysfunction and arterial pressure regulation during early diabetes in mice: roles for nitric oxide and endothelium-derived hyperpolarizing factor

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Abstract

On endothelial NO synthase (eNOS) and whether non-NO endothelium-dependent vasodilator mechanisms are altered in diabetes in mice. Male mice were instrumented for chronic measurement of mean arterial pressure (MAP). In wild-type mice, MAP was greater after 5 weeks of N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 mg.kg(-1).day(-1) in drinking water; 97+/-3 mmHg) than after vehicle treatment (88+/-3 mmHg). MAP was also elevated in eNOS null mice (113+/-4 mmHg). Seven days after streptozotocin treatment (200 mg/kg, iv) MAP was further increased in L-NAME-treated mice (108+/-5 mmHg), but not in vehicle treated mice (88+/-3 mmHg) or eNOS null mice (104+/-3 mmHg). In wild-type mice, maximal vasorelaxation of mesenteric arteries to acetylcholine was not altered by chronic L-NAME or induction of diabetes, but was reduced by 42+/-6 in L-NAME-treated diabetic mice. Furthermore, the relative roles of NO and endothelium-derived hyperpolarizing factor (EDHF) in acetylcholine-induced vasorelaxation were altered; the EDHF component was enhanced by L-NAME and blunted by diabetes. These data suggest that NO protects against the development of hypertension during early stage diabetes in mice, even in the absence of eNOS. Furthermore, in mesenteric arteries diabetes is associated with reduced EDHF function, with an apparent compensatory increase in NO function. Thus, prior inhibition of NOS results in endothelial dysfunction in early diabetes, since the diabetes-induced reduction in EDHF function cannot be compensated by increases in NO production. Key words: endothelial nitric oxide synthase, diabetes, L-NAME, endothelium-derived hyperpolarizing factor, endothelial function.
Original languageEnglish
Pages (from-to)R707 - R713
Number of pages7
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume293
Issue number2
Publication statusPublished - 2007

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