Differential effects of a nitric oxide donor on reperfusion-induced microvascular dysfunction in diabetic and non-diabetic rats

• Published in: Diabetologia Vol. 42; no. 11; pp. 1350 - 1358
• Main Authors: SALAS, A, PANES, J, ROSENBLOOM, C. L, ELIZALDE, J. I, ANDERSON, D. C, GRANGER, D. N, PIQUE, J. M
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.11.1999; Springer Nature B.V
• Subjects: Animals; Associated diseases and complications; Biological and medical sciences; Cell Adhesion - drug effects; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic Angiopathies - physiopathology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelium, Vascular - drug effects; Endothelium, Vascular - pathology; Endothelium, Vascular - physiopathology; Intercellular Adhesion Molecule-1 - metabolism; Ischemia - complications; Ischemia - physiopathology; Leukocytes - physiology; Male; Medical sciences; Microcirculation - drug effects; Nitric Oxide Donors - pharmacology; Nitrogen Oxides; Oxidative Stress - drug effects; Rats; Rats, Sprague-Dawley; Reperfusion Injury - complications; Reperfusion Injury - physiopathology; Spermine - analogs & derivatives; Spermine - pharmacology; Splanchnic Circulation - drug effects; Vasculitis - etiology; Vasculitis - physiopathology; Venules - drug effects; Venules - physiopathology; Endocrinopathy; Animal model; Intercellular adhesion molecule 1; Rat; Diabetes mellitus; Rodentia; Cardiovascular disease; Inflammation; Endothelium; Vascular disease; Microcirculation; Vertebrata; Mammalia; Reperfusion; Ischemia; Nitric oxide; Complication
• ISSN: 0012-186X; 1432-0428
• DOI: 10.1007/s001250051449

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. 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. 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. 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]