Trends in vascular pharmacology research in the Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine, Comenius University, Bratislava

Abstract

Research in the Department of Pharmacology started to focus intensively on fetal circulation in the 60s. Results of experiments contributed to clarification of the conversion of fetal circulation type to the adult type: the mechanism of the ductus arteriosus closure, examination of fetal and neonatal pulmonary vessel responses. In the early 80s, increased attention was dedicated to fetal vascular endothelium, later on to vascular reactivity in relation to the endothelium in adult animals. We developed original models of vascular endothelial damage using the perfusion method (repeated vasoconstrictive stimuli, deendothelization by air bubbles). We developed a new technique for in vitro endothelial loss quantification on Millipore filters. Under in vitro conditions, the protective effects of sulodexide and pentoxifylline on vascular endothelium were evaluated. In recent years were studied protective effects of selected substances in vivo in models of endothelial damage (e.g. stress, toxic tissue damage, diabetes mellitus, hypertension). The role of potassium channels in the hypertension model was studied in cooperation with the Czech Academy of Sciences. Assessment of vascular reactivity in the diabetic model was significantly improved by computer. In addition to experimental work, the department is solving problems of clinical pharmacology – especially drug risk evaluation (non-steroidal anti-inflammatory drugs). Recently, we have dealt with pharmacoepidemiological studies in geriatric patients and with cardiovascular risk of NSAIDs in relation to pharmacotherapy. The results of these studies may be an impulse for targeted problem solving in our experiments.

Alpha Lipoic Acid Treatment Improved Endothelium-dependent Relaxation in Diabetic Rat Aorta

“…15 18) The eŠects of diabetes on the vascular responsiveness of the rat aorta have been widely studied but there are con‰icting results. Although some researchers asserted that the response to ACh increases in diabetes, 8,19) the results of the present study, in accordance with others, 20 22) revealed that diabetes decreased the responses to ACh in maximum relaxation but not the sensitivity. The discrepancies could be due to diŠerences between diabetic models and/or the duration of the diabetes as mentioned by Pieper.…”

“…3,5 7) In addition, reduced endotheliumdependent relaxation to ACh was reported in rat mesenteric resistance arteries. 8) It was found that hyperglycemia induces reactive oxygen species (ROS) production mediating endothelial dysfunction. 9) Alpha-lipoic acid (ALA) is a nutritional dithiol compound and an essential cofactor in oxidative metabolism in the mitocondria.…”

Effect of sulodexide in patients with non-proliferative diabetic retinopathy: diabetic retinopathy sulodexide study (DRESS)

“…Vascular complications of DM are generally accompanied by development of endothelial dysfunction or injury, and in experimental models, this endothelial dysfunction or injury is manifested by an increased number of circulating endothelial cells. In vitro and animal models (rats with streptozotocin-induced diabetes) of endothelial injury/dysfunction have reported that sulodexide was able to repair or prevent the endothelial damage, lower the number of circulating endothelial cells, and improve the endothelium-dependent relaxation of small arteries [ 23 – 25 ]. Recently, it was proved that oral sulodexide administration in patients with type 2 DM enhances the availability of precursors for GAG synthesis, thereby improving the endothelial glycocalyx dimension in sublingual and retinal vascular beds.…”

Effect of grape seed proanthocyanidin extract on hard exudates in patients with non-proliferative diabetic retinopathy

“…Song et al (DRESS study group) conducted a clinical trial with a similar design to our study and suggested that oral sulodexide, which is a highly purified glycosaminoglycan (GAG), showed a significant decrease in HEs in patients with mild to moderate NPDR, with central foveal thickness ≤300 μm. [19] Based on previous animal study, [24] they presumed that oral sulodexide may repair endothelial damage due to diabetes and normalize the vascular permeability and GAG metabolism, resulting in resorption of HEs. They reported that oral sulodexide did not show significant differences in central retinal thickness compared to the placebo group.…”