Vojtko R

Long-term Treatment with Hesperidin Improves Endothelium-dependent Vasodilation in Femoral Artery of Spontaneously Hypertensive Rats: The Involvement of NO-synthase and Kv Channels.

Hesperidin is the most common flavonoid found in citrus fruits and is expected to exert vasodilation action relevant to its health benefits. The present study aimed to explore the effect of hesperidin on the vascular responses in normotensive and hypertensive rats and the involvement of NO‐synthase and Kv channels. The 15‐week‐old Wistar and spontaneously hypertensive rats (SHR) were randomized to orally receive either hesperidin (50 mg/kg/day) or a corresponding volume of the water for 4 weeks. Vascular responses of isolated femoral arteries were studied with myograph in control conditions and during inhibition of NO‐synthase with l‐NNA and Kv channels with 4‐AP. Hesperidin had no effect on blood pressure. Endothelium‐dependent vasodilation in Wistar and SHR was significantly improved by the treatment with hesperidin. The contraction responses after l‐NNA were increased in all groups of rats to similar extent, but relaxatory responses were significantly attenuated only in SHR. The inhibition of Kv channels significantly reduced endothelium‐dependent vasodilatory responses in only in SHR administered with hesperidin. The results of our experiment indicate that hesperidin might improve the endothelium‐dependent vasodilation during hypertension, possibly through the enhancement of Kv channels function. Copyright

Vascular reactivity of arteria femoralis in adult and aged spontaneously hypertensive and Wistar-Kyoto rats.

AIM The relationship of age and hypertension on endothelial dysfunction and increased responses to vasoconstrictor stimuli. BACKGROUND Hypertension is a disease accompanied by endothelial dysfunction and is characterized by an impaired vascular reactivity and enhanced activity of sympathetic nervous system. MATERIALS AND METHODS In our experiment, we used spontaneously hypertensive rats representing model of essential hypertension and the Wistar-Kyoto rats as normotensive strain. Femoral arteries of adult and aged rats were put into the chamber of Mulvany-Halpern isometric myograph. As the nutrient solution, the modified Krebs-Henseleit solution having temperature 37 °C and bubbled with O2 was used. After 30 minutes stabilization of blood vessels, a dose-dependent curve of norepinephrine response was recorded (concentrations 3x10-8 M, 10-7 M, 3x10-7 M, 10-6 M, 3x10-6 M, 10-5 M, 3x10-5 M, 10-4 M), followed by a dose-dependent curve of acetylcholine response (concentrations 3x10-8 M, 10-7 M, 3x10-7 M, 10-6 M, 3x10-6 M). RESULTS Our experiments recorded an increased reactivity to contraction stimuli in spontaneously hypertensive animals. Vascular reactivity to norepinephrine at 5 month and 12 month old rats from the same group was not significantly affected. Our experiments on the other hand, did not record a reduced endothelium-dependent relaxation in hypertensive compared to normotensive animals, neither in different age groups. CONCLUSIONS Increased norepinephrine-induced contraction occurs even before development of reduced acetylcholine-induced relaxation in SHR rats. We predict that in our experiment hypertension plays a bigger role in the development of endothelial dysfunction than aging (Fig. 2, Ref. 22).

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

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