Effect of sacubitril/valsartan on the hypertensive heart in continuous light-induced and lactacystin-induced pre-hypertension: Interactions with the renin-angiotensin-aldosterone system
Language English Country France Media print-electronic
Document type Journal Article
PubMed
38461685
DOI
10.1016/j.biopha.2024.116391
PII: S0753-3322(24)00275-0
Knihovny.cz E-resources
- Keywords
- Angiotensin/aldosterone, Continuous light, Lactacystin, Pre-hypertension, Remodelling, Sacubitril/valsartan/ARNI,
- MeSH
- Acetylcysteine analogs & derivatives MeSH
- Aldosterone MeSH
- Aminobutyrates * MeSH
- Biphenyl Compounds pharmacology MeSH
- Fibrosis MeSH
- Drug Combinations MeSH
- Hypertension * drug therapy MeSH
- Hypertrophy, Left Ventricular MeSH
- Rats MeSH
- Rats, Wistar MeSH
- Prehypertension * MeSH
- Renin-Angiotensin System MeSH
- Renin MeSH
- Heart Failure * MeSH
- Stroke Volume MeSH
- Tetrazoles pharmacology therapeutic use MeSH
- Valsartan pharmacology MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- Acetylcysteine MeSH
- Aldosterone MeSH
- Aminobutyrates * MeSH
- Biphenyl Compounds MeSH
- Drug Combinations MeSH
- lactacystin MeSH Browser
- Renin MeSH
- sacubitril MeSH Browser
- Tetrazoles MeSH
- Valsartan MeSH
This study investigated whether sacubitril/valsartan or valsartan are able to prevent left ventricular (LV) fibrotic remodelling and dysfunction in two experimental models of pre-hypertension induced by continuous light (24 hours/day) exposure or by chronic lactacystin treatment, and how this potential protection interferes with the renin-angiotensin-aldosterone system (RAAS). Nine groups of three-month-old male Wistar rats were treated for six weeks as follows: untreated controls (C), sacubitril/valsartan (ARNI), valsartan (Val), continuous light (24), continuous light plus sacubitril/valsartan (24+ARNI) or valsartan (24+Val), lactacystin (Lact), lactacystin plus sacubitil/valsartan (Lact+ARNI) or plus valsartan (Lact+Val). Both the 24 and Lact groups developed a mild but significant systolic blood pressure (SBP) increase, LV hypertrophy and fibrosis, as well as LV systolic and diastolic dysfunction. Yet, no changes in serum renin-angiotensin were observed either in the 24 or Lact groups, though aldosterone was increased in the Lact group compared to the controls. In both models, sacubitril/valsartan and valsartan reduced elevated SBP, LV hypertrophy and fibrosis and attenuated LV systolic and diastolic dysfunction. Sacubitril/valsartan and valsartan increased the serum levels of angiotensin (Ang) II, Ang III, Ang IV, Ang 1-5, Ang 1-7 in the 24 and Lact groups and reduced aldosterone in the Lact group. We conclude that both continuous light exposure and lactacystin treatment induced normal-to-low serum renin-angiotensin models of pre-hypertension, whereas aldosterone was increased in lactacystin-induced pre-hypertension. The protection by ARNI or valsartan in the hypertensive heart in either model was related to the Ang II blockade and the protective Ang 1-7, while in lactacystin-induced pre-hypertension this protection seems to be additionally related to the reduced aldosterone level.
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