ANTIHYPERTENSIVE AND CARDIOPROTECTIVE EFFECTS OF EPOXYEICOSATRIENOIC ACID ANALOGS AND SOLUBLE EPOXIDE HYDROLASE...

Area of Science:

• Cardiovascular Pharmacology
• Renal Physiology
• Molecular Medicine

Background:

• Epoxieicosatrienoic acids (EETs), derived from arachidonic acid, regulate arterial pressure and exhibit diverse biological activities in the vasculature, heart, and kidneys.
• Soluble epoxide hydrolase (sEH) is a key enzyme in EET metabolism, making it a potential therapeutic target for cardiovascular diseases.

Purpose of the Study:

• To investigate the antihypertensive and cardioprotective effects of epoxieicosatrienoic acids (EETs) analogues and soluble epoxide hydrolase (sEH) inhibitors.
• To elucidate the mechanisms underlying the beneficial actions of EETs and sEH inhibitors in models of arterial hypertension.

Main Methods:

• Administration of EETs analogues and sEH inhibitors in experimental models of arterial hypertension, including Dahl-salt-sensitive rats.
• Assessment of cardiovascular and renal parameters, including blood pressure, inflammation markers, oxidative stress, and fibrotic changes.
• In vitro studies using cultured endothelial cells to evaluate anti-inflammatory actions.

Main Results:

• EETs analogues demonstrated renoprotective effects, reducing inflammation and fibrosis in the heart and kidneys of hypertensive rats.
• sEH inhibitors significantly reduced arterial pressure in experimental models, associated with anti-inflammatory and renoprotective actions.
• EETs exhibited anti-inflammatory properties in endothelial cells and showed potential interaction with PPARγ receptors.

Conclusions:

• EETs and sEH inhibitors represent promising therapeutic strategies for managing arterial hypertension and its associated cardiovascular and renal complications.
• Targeting the EETs/sEH pathway offers a novel approach to restoring vascular homeostasis and protecting organ function in hypertensive states.