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Title: Evaluation of new compounds with α1 adrenolytic activity in experimental models of hypertension

Author:

Nowińska, Katarzyna

Date:

2017

Type:

Praca doktorska

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 results 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.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

choroby układu krążenia

Degree grantor:

Uniwersytet Jagielloński. Collegium Medicum. Wydział Farmaceutyczny. Zakład Wstępnych Badań Farmakologicznych Katedry Farmakodynamiki.

Promoter:

Jacek Sapa ; Marek Bednarski

Date issued:

2017

Identifier:

oai:dl.cm-uj.krakow.pl:4280

Call number:

ZB-127565

ControlNumberVIRTUA:

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Access rights:

nieograniczony

Location of original object:

Biblioteka Medyczna Uniwersytetu Jagiellońskiego- Collegium Medicum

Subject and keywords:

models of hypertension hypertension α1 adrenolytics L-NAME

Object collections:

Last modified:

May 10, 2019

In our library since:

May 6, 2019

Number of object content hits:

19

All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/4281

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Edition name Date
ZB-127565 May 10, 2019

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