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Evaluation of endothelium-protective effects of drugs in experimental models of endothelial damage
V Kristová1, M Kriska, P Babál
1Department of Pharmacology, Faculty of Medicine, Comenius University, Bratislava, Slovak Republic. farmakologia@fmed.uniba.sk
Abstract:
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 x l(-1)) 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 microg: 32.25 vs. 14.25, at dose 1 microg: 51 vs. 27.75 (p<0.01), at dose 10 microg 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 microg 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.
Insights
Pentoxifylline (PTX) and sulodexide (SLX) demonstrate endothelium-protective effects. PTX reduced vasoconstriction caused by noradrenaline (NA) in the presence of polymorphonuclear leukocytes (PMN), while SLX decreased endothelial cell damage induced by NA.
Area of Science:
- Pharmacology
- Vascular Biology
- Cell Biology
Background:
- Endothelial dysfunction and injury are critical in vascular diseases.
- Pharmacological agents can protect the endothelium.
- Experimental models are essential for evaluating these protective properties.
Purpose of the Study:
- To evaluate the endothelium-protective effects of pentoxifylline (PTX) and sulodexide (SLX).
- To assess PTX's impact on noradrenaline (NA)-induced vasoconstriction in a polymorphonuclear leukocyte (PMN)-induced endothelial dysfunction model.
- To determine SLX's efficacy in preventing endothelial damage induced by repeated NA administration.
Main Methods:
- Rabbit renal artery model of endothelial dysfunction induced by PMN perfusion.
- Assessment of NA-induced vasoconstrictor responses with and without PTX.
- Rabbit model of endothelial damage induced by repeated NA administration.
- Quantification of desquamated endothelial cells (EC) with and without SLX.
Main Results:
- PMN perfusion significantly increased NA-induced vasoconstriction.
- PTX significantly diminished NA-induced vasoconstrictor responses in PMN-perfused vessels.
- SLX significantly reduced the number of desquamated EC compared to controls.
- PTX and SLX demonstrated favorable endothelium-protective effects in their respective models.
Conclusions:
- Pentoxifylline exhibits endothelium-protective properties by mitigating vasoconstriction in a PMN-induced dysfunction model.
- Sulodexide demonstrates endothelium-protective effects by reducing endothelial cell damage.
- These findings support the therapeutic potential of PTX and SLX in conditions involving endothelial dysfunction or injury.
