Captopril alleviates vascular endothelial dysfunction by regulating TRPV1 and activating the eNOS pathway

Area of Science:

• Cardiovascular Pharmacology
• Diabetology
• Endothelial Biology

Background:

• Diabetic cardiovascular complications are linked to vascular endothelial dysfunction (VED).
• The precise mechanisms by which Captopril (CAP) ameliorates diabetic VED are not fully understood.

Purpose of the Study:

• To identify key targets and pathways involved in CAP's effects on diabetic VED.
• To elucidate the role of the TRPV1/eNOS pathway in CAP's therapeutic action.

Main Methods:

• Network pharmacology and protein-protein interaction (PPI) analyses to identify targets.
• In vivo studies in diabetic rats to assess CAP's effects on vascular permeability, nitric oxide (NO), and reactive oxygen species (ROS).
• In vitro studies using high glucose-exposed C166 cells treated with CAP, with or without TRPV1 antagonist, to evaluate TRPV1/eNOS expression and endothelial function.

Main Results:

• Network analysis identified eNOS, HSP90A, and PPARG as central targets.
• In vivo, CAP improved vascular permeability, reduced ROS, and increased NO, with enhanced TRPV1 and eNOS expression.
• In vitro, CAP restored TRPV1/eNOS expression, elevated NO, mitigated oxidative stress, and improved endothelial barrier function, effects abolished by TRPV1 inhibition.

Conclusions:

• CAP alleviates diabetic VED through a TRPV1-dependent mechanism.
• Activation of the TRPV1/eNOS pathway by CAP attenuates oxidative stress and restores endothelial function.
• CAP shows potential as a therapeutic agent for diabetic endothelial dysfunction.