Evaluation of Endothelium-Protective Effects of Drugs in Experimental Models of Endothelial Damage

V. Kristová, M. Kriška, P. Babál¹, M. N. Djibril, J. Slámová, A. Kurtanský²

Received July 30, 1999
Accepted September 21, 1999

Summary
Endothelium-protective properties of pharmacological agents may be assessed by using different experimental models of endothelial dysfunction or injury. The model of endothelial dysfunction induced by vessel perfusion with polymorphonuclear leukocytes (PMN) was used for evaluation of pentoxifylline (PTX) effects on vasoconstrictor responses to noradrenaline (NA) in the rabbit renal artery. Addition of PMN into the perfusion solution significantly increased the responses to NA at all doses. PTX administration (10^-5 mol.l¹) significantly diminished the constrictor responses to NA in vessels perfused with PMN+PTX when compared to the responses in PMN-perfused vessels (at dose 0.1 m g: 32.25 vs. 14.25, at dose 1 m g: 51 vs. 27.75 (p<0.01), at dose 10 m g 74.25 vs. 39.75 (p<0.05), all values expressed as median of perfusion pressure in mm Hg). The model of endothelial damage induced by repeated NA administration in 5 doses (10-50 m g of NA) was used for evaluation of the endothelium-protective effect of sulodexide (SLX). It was found that SLX (120 U/l) significantly decreased the number of desquamated endothelial cells (EC) compared to the control group (controls: 131.4± 20.1 EC, +SLX: 83.3± 13.8 EC, p<0.01). These results confirmed the favorable endothelium-protective effects of pentoxifylline and sulodexide in the two experimental models.

Key words
Models of endothelial dysfunction and damage · Endothelium-protective effects · Sulodexide · Pentoxifylline

Reprint requests
V. Kristová, M.D., Ph.D., Department of Pharmacology, Faculty of Medicine, Comenius University, Sasinkova 4, 813 72 Bratislava, Slovak Republic, e-mail: farmakologia@fmed.uniba.sk.