caa a22 4500 475771923 CHVBK 20180406123619.0 cr unu---uuuuu 170329e20000301xx s 000 0 eng 10.1007/s001250050052 doi (NATIONALLICENCE)springer-10.1007/s001250050052 Gene transfer of endothelial nitric oxide synthase alters endothelium-dependent relaxations in aortas from diabetic rabbits [Elektronische Daten] [M. Zanetti, J. Sato, Z. S. Katusic, T. O'Brien] Aims/hypothesis. Cardiovascular disease is the leading cause of death in diabetes mellitus. Abnormal endothelium-dependent relaxation is observed both in humans and in animal models of diabetes mellitus and decreased bioavailability of nitric oxide (NO) is thought to be involved in this defect. Therefore, the aim of this study was to test whether adenovirus-mediated gene transfer of endothelial nitric oxide synthase (eNOS) alters vascular reactivity of diabetic vessels.¶Methods. Vascular reactivity was first assessed in thoracic aortas and carotid arteries from nine alloxan-induced diabetic (plasma glucose, 26.5 ± 1.2 mmol/l; HbA1 c, 6.4 ± 0.3 %) and nine control rabbits (plasma glucose, 11.1 ± 1.3 mmol/l; HbA1 c, 2.1 ± 0.1 %). Vascular reactivity was next examined in thoracic aortas of diabetic animals after ex vivo transduction with replication-deficient adenovirus encoding gene for eNOS (AdeNOS) or β-galactosidase (Adβ gal).¶Results. After 10 weeks of hyperglycaemia, endothelium-dependent relaxation to acetylcholine was impaired in diabetic aorta, but was normal in carotid arteries from diabetic rabbits. In contrast, responses of both vessels to calcium ionophore and nitric oxide donor were normal. Histochemical staining for β-galactosidase and immunohistochemistry for eNOS showed transgene expression in the endothelium and adventitia in Adβ gal and AdeNOS transduced vessels, respectively. During submaximum contractions with phenylephrine, relaxations to low concentrations of acetylcholine (3 × 10-8 to 10-7 mol/l) were augmented in AdeNOS transduced diabetic vessels.¶Conclusion/interpretation. These findings suggest that adenovirus-mediated gene transfer of eNOS to diabetic aorta alters vascular reactivity. [Diabetologia (2000) 43: 340-347] Springer-Verlag Berlin Heidelberg, 2000 Keywords Gene transfer, nitric oxide synthase, adenovirus, endothelium, diabetes mellitus, alloxan, nitric oxide nationallicence Zanetti M. Department of Endocrinology, Mayo Clinic and Foundation, Rochester, Minnesota, USA, US aut Sato J. Department of Endocrinology, Mayo Clinic and Foundation, Rochester, Minnesota, USA, US aut Katusic Z. S. Department of Anaesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota, USA, US aut O'Brien T. Department of Endocrinology, Mayo Clinic and Foundation, Rochester, Minnesota, USA, US aut https://doi.org/10.1007/s001250050052 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s001250050052 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Zanetti M. Department of Endocrinology, Mayo Clinic and Foundation, Rochester, Minnesota, USA, US aut NATIONALLICENCE 700 1- Sato J. Department of Endocrinology, Mayo Clinic and Foundation, Rochester, Minnesota, USA, US aut NATIONALLICENCE 700 1- Katusic Z. S. Department of Anaesthesiology, Mayo Clinic and Foundation, Rochester, Minnesota, USA, US aut NATIONALLICENCE 700 1- O'Brien T. Department of Endocrinology, Mayo Clinic and Foundation, Rochester, Minnesota, USA, US aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer