Vasodilator prostaglandins (PGE2, PGI2) play an important role in the regulation of renal blood flow. Hence, inhibition of their production with nonsteroidal anti-inflammatory drugs increases renal vascular resistance and exerts adverse renal effects. It has been reported that besides endothelium-derived prostaglandin products, nitric oxide (NO) may be mainly involved in regulation of renal functions. The aim of our study was to evaluate the effect of cyclooxygenase inhibition with indomethacin and endothelium removal on vascular responses of the renal artery as a model vessel. Isolated segments of rabbit renal arteries were perfused at constant flow. Indomethacin administration (10-5mol.l-1) significantly increased the responses to single doses (0.1, 1, 10 m g) of noradrenaline (NA) as compared with the controls. In indomethacin-pretreated vessels, subsequent deendothelisation by air bubbles enhanced the constrictor responses to NA. In reversed order, when deendothelisation was followed by indomethacin administration, the responses to NA were similar in character. A comparison of renal artery responses to NA in both experimental situations did not reveal any significant differences. It can be supposed that endothelial and non-endothelial factors may be involved in local regulation of renal vascular tone., V. Kristová, M. Kriška, R. Vojtko, A. Kurtanský., and Obsahuje bibliografii
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., V. Kristová, M. Kriška, P. Babál, M. N. Djibril, J. Slámová, A. Kurtanský., and Obsahuje bibliografii
Diabetes mellitus is associated with many complications including retinopathy, nephropathy, neuropathy and angiopathy. Increased cardiovascular risk is accompanied with diabetes-induced endothelial dysfunction. Pharmacological agents with endothelium-protective effects may decrease cardiovascular complications. In present study sulodexide (glycosaminoglycans composed from heparin-like and dermatan fractions) was chosen to evaluate its protective properties on endothelial dysfunction in diabetes. Effect of sulodexide treatment (SLX, 100 UI/kg/day, i.p.) in 5 and 10 weeks lasting streptozotocin-induced diabetes (30 mg/kg/day, i.p. administered for three consecutive days) was investigated. Animals were divided into four groups: control (injected with saline solution), control-treated with sulodexide (SLX), diabetic (DM) and diabetic-treated with sulodexide (DM+SLX). The pre-prandial and postprandial plasma glucose levels, number of circulating endothelial cells (EC) and acetylcholine-induced relaxation of isolated aorta and mesenteric artery were evaluated. Streptozotocin elicited hyperglycemia irrespective of SLX treatment. Streptozotocin-induced diabetes enhanced the number of circulating endothelial cells compared to controls. SLX treatment decreased the number of EC in 10-week diabetes. Acetylcholine-induced relaxation of mesenteric arteries was significantly impaired in 5 and 10-week diabetes. SLX administration improved relaxation to acetylcholine in 5 and 10-week diabetes. Diabetes impaired acetylcholine-induced relaxation of rat aorta irrespective of SLX treatment. Our results demonstrate that SLX treatment lowers the number of circulating endothelial cells and improves endothelium-dependent relaxation in small arteries. These findings suggest endothelium-protective effect of sulodexide in streptozotocin-induced diabetes., V. Kristová, S. Líšková, R. Sotníková, R. Vojtko, A. Kurtanský., and Obsahuje bibliografii a bibliografické odkazy