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Influence of tolrestat on the defective leukocyte-endothelial interaction in experimental diabetes.
- Source :
-
European journal of pharmacology [Eur J Pharmacol] 2000 Mar 10; Vol. 391 (1-2), pp. 163-74. - Publication Year :
- 2000
-
Abstract
- One of the most devastating secondary complications of diabetes is the blunted inflammatory response that becomes evident even in the very early stages of poorly controlled diabetes mellitus. While the etiology of this diminished response is not clearly understood, it has been linked to a decrease in the respiratory burst of neutrophils, as well as a decrease in microvessel response to inflammatory mediators and defective leukocyte-endothelial interactions. Using video microscopy to visualize vessels of the internal spermatic fascia, we have characterized leukocyte-endothelial interactions in alloxan-induced diabetic and in galactosemic rats by quantitating the number of leukocytes rolling along the venular endothelium and the number of leukocytes sticking to the vascular wall after topical application of zymosan-activated plasma or leukotriene B(4) (1 ng/ml), as well as after the application of a local irritant stimulus (carrageenan, 100 microg). We observed that while 33 days of alloxan-induced diabetes or 7 days of galactosemia had no effect on total or differential leukocyte counts and on the wall shear rate, both treatments significantly (P<0.001) reduced the number of leukocytes rolling along the venular endothelium by about 70% and the number of adhered leukocytes in postcapillary venules by 60%. These effects were not observed in diabetic and galactosemic animals treated with an aldose reductase inhibitor. The results suggest that impaired leukocyte-endothelial cell interactions are a consequence of an enhanced flux through the polyol pathway.
- Subjects :
- Animals
Blood Glucose metabolism
Body Weight drug effects
Carrageenan pharmacology
Cell Migration Inhibition
Cell Movement drug effects
Endothelium, Vascular cytology
Hemodynamics drug effects
Interleukin-16 pharmacology
Leukocyte Count drug effects
Male
Rats
Rats, Wistar
Receptors, Leukocyte-Adhesion drug effects
Spermatic Cord cytology
Spermatic Cord drug effects
Aldehyde Reductase antagonists & inhibitors
Diabetes Mellitus, Experimental physiopathology
Endothelium, Vascular drug effects
Enzyme Inhibitors pharmacology
Leukocytes drug effects
Naphthalenes pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 0014-2999
- Volume :
- 391
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- European journal of pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 10720648
- Full Text :
- https://doi.org/10.1016/s0014-2999(00)00057-1