ESPN 51th Annual Meeting

ESPN 2018


 
The activation of the local skin renin-angiotensin system following dietary salt overload
TIVADAR TULASSAY 2 DáNIEL SUGáR 1 RóBERT AGóCS 1 DOMONKOS PAP 2 ENDRE SULYOK 3

1- 1ST DEPARTMENT OF PEDIATRICS, SEMMELWEIS UNIVERSITY, BUDAPEST, HUNGARY.
2- MTA-SE PEDIATRICS AND NEPHROLOGY RESEARCH GROUP, BUDAPEST, HUNGARY.
3- FACULTY OF HEALTH SCIENCES, UNIVERSITY OF PéCS, PéCS, HUNGARY.
 
Introduction:

Dietary sodium bound to the negatively charged glycosaminoglycan (GAG) molecules of the skin may modulate the local renin–angiotensin system (RAS), thus initiating tissue remodeling and vasoconstriction. We investigated the regulation and activation of the components of the local skin RAS, and their effect on blood pressure and sodium handling in a salt overloaded rat model.

Material and methods:

Thirty-six eight-week-old male Sprague Dawley rats were fed either on low salt (LSD, NaCl<0,01% m/m, n=12), normal salt (NSD, NaCl= 0,3% m/m, n=12) or high salt (HSD, NaCl = 8% m/m, n=12) diet for 4 weeks. Body weight, blood pressure, food and water consumption, urine volume and its electrolyte composition were measured during the whole length of the experiment. Tissue samples were collected for molecular investigations (qRT-PCR, western blot, immunhistochemistry) at 4 weeks.

Results:

By week 3, significant rise in systolic blood pressure was detected in HSD group comparing to NSD and LSD (131,9±9,4;114,5±4,2;114,5±6,5mmHg respectively, p<0.01). Daily water consumption, urine volume and Na-excretion was higher and body weight was lower in HSD group. Elevated levels of skin angiotensinogen (AGT) mRNA levels were detected in the HSD group compared to the NSD group (p<0,05). Neither the mRNA levels of prorenin receptor (PRR) nor mRNA level of angiotensin converting enzyme (ACE) 1 and 2 exhibited significant changes. Salt load induced increased skin TGF-beta mRNA expression (p<0,05).

Conclusions:

The elevated skin AGT mRNA level, and the lack of decrease in the level of ACE expression implies the activation of the skin local RAS system per se. The increase in TGF-beta mRNA expression may point to the salt-induced tissue remodeling and fibrosis. Further investigations are needed to describe the role of the complex RAS components (renin, angiotensin 1 and 2 receptor), as well as the interaction between RAS and TGF-beta pathway.