Differential effects of a nitric oxide donor on reperfusion-induced microvascular dysfunction in diabetic and non-diabetic rats
| Autor: | D C Anderson, C. L. Rosenbloom, J I Elizalde, D. N. Granger, Azucena Salas, J M Piqué, Julián Panés |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Vasculitis medicine.medical_specialty P-selectin Endothelium Endocrinology Diabetes and Metabolism Ischemia Inflammation Diabetes Mellitus Experimental Microcirculation Nitric oxide Rats Sprague-Dawley chemistry.chemical_compound Venules Diabetes mellitus Internal medicine medicine.artery Cell Adhesion Leukocytes Internal Medicine medicine Animals Nitric Oxide Donors Splanchnic Circulation Superior mesenteric artery business.industry Intercellular Adhesion Molecule-1 medicine.disease Rats Oxidative Stress medicine.anatomical_structure Endocrinology chemistry Reperfusion Injury Immunology Nitrogen Oxides Spermine Endothelium Vascular medicine.symptom business Diabetic Angiopathies |
| Zdroj: | Diabetologia. 42:1350-1358 |
| ISSN: | 1432-0428 0012-186X |
| DOI: | 10.1007/s001250051449 |
| Popis: | Aims/hypothesis. Diabetes is associated with a high incidence of ischaemic disease and impaired nitric oxide responses. Therefore, the aim of the present study was to assess the effect of nitric oxide on ischaemia/reperfusion (I/R)-induced microvascular responses in an experimental model of diabetes. Methods. Leucocyte-endothelial cell interactions were studied in mesenteric venules after superior mesenteric artery occlusion (10 min), at 10 and 30 min of reperfusion in control and streptozotocin-induced diabetic rats. An oxidant-sensitive fluorochrome was used to measure oxidant production during reperfusion. P-selectin and ICAM-1 expression were quantified at 10 and 30 min of reperfusion respectively, using radiolabelled monoclonal antibodies. The transcription of ICAM-1 mRNA was determined by northern blot. The effect of spermine NONOate, given locally, on all variables studied, was assessed in additional experiments. Results. Ischaemia/reperfusion induced an enhanced leucocyte accumulation and oxidant production in diabetic animals. Moreover, I/R enhanced endothelial P-selectin expression in both groups of animals, whereas it only up regulated ICAM-1 endothelial expression and mRNA expression in diabetic rats. Spermine NONOate abrogated to a similar extent leucocyte adhesion and emigration in control and diabetic animals, although the mechanisms underlying this protective effect appear to be different. In control rats Spermine NONOate effectively prevented P-selectin up regulation, whereas in diabetic rats NO appreciably attenuated the rapid up regulation of ICAM-1 by preventing its transcription. Conclusions/interpretation. Expression of ICAM-1 is rapidly increased in diabetic, but not control, animals exposed to I/R. The increased endothelial cell adhesion molecule expression, leucocyte-endothelial cell adhesion and oxidant stress induced by I/R in diabetic rats are significantly attenuated by exogenous NO. [Diabetologia (1999) 42: 1350–1358] |
| Databáze: | OpenAIRE |
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