Institutional creator:

Instytut Medycyny Doświadczalnej i Klinicznej im. Mirosława Mossakowskiego PAN

Contributor:

Koźniewska- Kołodziejska, Ewa (Promotor) ; Olszyński, Krzysztof H. (Promotor pomocniczy)

Place of publishing:

Warszawa

Degree name:

doktor

Level of degree:

2

Degree discipline :

nauki medyczne

Degree grantor:

Instytut Medycyny Doświadczalnej i Klinicznej im. M. Mossakowskiego PAN

Abstract:

A high-sodium diet is one of the important risk factors for developing cardiovascular diseases, including high blood pressure and stroke. The mechanisms underlying the increase in blood pressure due to high sodium intake is not well understood. The results of experimental studies of the last decades on the effect of a highsodium diet on the circulatory system have drawn the attention of researchers to the vascular system of renin-angiotensin (RAS). This is one of the tissue systems where Ang I is converted to Ang II locally with a help of serine proteases such as chymase. Additionally, it was shown that an increase in the concentration of sodium ions in the extracellular environment reduces the sensitivity of endothelial cells to mechanical deformation (endothelial stiffening) and reduces the secretion of nitric oxide (NO) in response to shear stress. Based on in vitro studies, an increased concentration of sodium ions are due to damage to the glycocalyx of the endothelium. This leads to endothelial dysfunction which results in reduced NO secretion. The consequence of endothelial stiffening and glycocalyx damage is an increase in vascular resistance and an increase in blood pressure. Studies on the effect of a high-sodium diet and sodium-dependent hypertension on the regulation of resistance blood vessel are fragmentary, and conclusions are often derived from ex vivo studies on cell cultures of cells that are constituents of the vessel wall. It is not known to what extent the changes occurring in the resistance vessels in the course of sodium-dependent hypertension are conditioned by the increased supply of sodium in the diet, and to what extent by hypertension itself. It is also unknown whether and to what extent the renin-angiotensin vascular system is involved in the development or maintenance of sodium-dependent hypertension. Examination of the latter issue seems to be particularly important from the point of view of some problems associated with the treatment of human hypertension with ACE inhibitors. Long-term treatment with drugs from this group loses effectiveness in about 15% of patients. This phenomenon is called 'angiotensin escape' and is characterized by a progressive increase in plasma Ang II levels despite continued treatment. Therefore, it seems reasonable to search for drugs that inhibit the formation of angiotensin II independent of ACE inhibitors. Thus the aim of this project was to test the following hypotheses: 1. A long-term high-sodium diet causes functional changes: I. in peripheral resistance blood vessels, which have a significant impact on the development of sodium-dependent arterial hypertension; II. in the middle cerebral artery, leading to impairment of endothelium-dependent regulation of cerebral circulation; 2. Long-term high-sodium diet adversely affects the intestinal microbiota, leading to excessive production of trimethylamine (TMA) and its oxidized derivative TMAO; 3. The development of sodium-dependent hypertension is associated with the activation of both plasma and local renin-angiotensin system; 4. Chymase inhibitors are more effective than ACE inhibitors as hypotensive therapy in sodium-dependent hypertension. Concluding, the obtained results indicate that high sodium diet, even if it is not accompanied by an increase in plasma sodium ions concentration and hypertension, leads to endothelial dysfunction demonstrated both in peripheral and cerebral resistance arteries. Moreover, a high sodium diet enhances the response to vasoconstrictors of peripheral but not cerebral resistance arteries. Both plasma and tissue renin-angiotensin systems are involved in the development of sodium-dependent hypertension, however, blocking the tissue system seems to be more effective in lowering blood pressure than blocking the blood plasma RAS.

Detailed Resource Type:

PhD Dissertations

Resource Identifier:

oai:rcin.org.pl:240872

Source:

IMDiK PAN, ZS 432 ; click here to follow the link

Language:

pol

Language of abstract:

eng

Rights:

Creative Commons Attribution BY 4.0 license

Terms of use:

Copyright-protected material. [CC BY 4.0] May be used within the scope specified in Creative Commons Attribution BY 4.0 license, full text available at: ; -

Digitizing institution:

Mossakowski Medical Research Institute PAS

Original in:

Library of the Mossakowski Medical Research Institute PAS

Projects co-financed by:

Operational Program Digital Poland, 2014-2020, Measure 2.3: Digital accessibility and usefulness of public sector information; funds from the European Regional Development Fund and national co-financing from the state budget.

Access:

Open