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Title: Evaluation of new compounds with α1 adrenolytic activity in experimental models of hypertension
Abstract:
The aim of this doctoral study was evaluation of hypotensive and pleiotropic activity of tested compounds after chronic administration in the selected experimental models of hypertension. Seven compounds with α1-adrenolytic activity were selected for tests, three of which were xanthone derivatives (MH-2, MH-3 and MH-99) and others four were pyrrolidin-2-one derivatives (EP-46, EP-47, EP-49 and EP-58). The main aim of this study required validation of four different animal models of hypertension: DEX model, DOCA model, FRU model and L-NAME model. This last one – L-NAME model – met all assumptions of this study and was selected to evaluation of potential pleiotropic activities of tested compounds. All of tested compounds were evaluated in L-NAME model after chronic administration in terms of their potential hypotensive activity, influence on relaxation of isolated rat-aorta, on glucose and lipid plasma levels, on oxidative stress parameters, on NO2- and NO3- plasma levels, and also on two circulatory biomarker plasma levels – ADMA and VEGF. At the end intrinsic activity for tested compounds towards human α1A-, α1B- and α1D-adrenoceptors was also evaluated. Compounds marked with symbols MH-2, MH-3 and MH-99 showed high therapeutic activity in all pharmacological and biochemical studies. Additionally, these compounds showed also high preferential α1D-adrenolytic activity. These res ; ults suggest that α1D-adrenolytic activity of tested compound may be connected with their hypotensive activity and with their corrective influence on disturbed endothelium function induced in L-NAME hypertension model.
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Sapa, Jacek ; Bednarski, Marek
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Last modified:
Jun 26, 2023
In our library since:
May 6, 2019
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100
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96
All available object's versions:
http://dl.cm-uj.krakow.pl:8080/publication/4281
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| Edition name | Date |
|---|---|
| ZB-127565 | Jun 26, 2023 |
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