κ-Opioid Receptors Improve Vascular Endothelial Dysfunction in Salt-Sensitive Hypertension via PI3K/Akt/eNOS...

Area of Science:

• Cardiovascular Pharmacology
• Endothelial Biology
• Hypertension Research

Background:

• Kappa-opioid receptors (κ-OR) play a role in cardiovascular regulation.
• Endothelial dysfunction is a key feature of salt-sensitive hypertension.
• The specific mechanisms of κ-OR in this context require further elucidation.

Purpose of the Study:

• To investigate the effects of κ-OR activation on endothelial dysfunction in a rat model of salt-sensitive hypertension.
• To elucidate the underlying molecular mechanisms, including the PI3K/Akt/eNOS pathway.

Main Methods:

• A rat model of salt-sensitive hypertension was established using a high-salt diet.
• Rats were treated with a κ-OR activator (U50,488H) or inhibitor (nor-BNI).
• Vascular function, oxidative stress markers, and protein expression (NOS, Akt, eNOS, Caveolin-1) were assessed in vivo and in vitro.

Main Results:

• κ-OR activation (U50,488H) improved vasodilation, increased nitric oxide (NO), and decreased inflammatory markers.
• U50,488H treatment reduced endothelial cell apoptosis and injury, and enhanced antioxidant capacity.
• Activation of the PI3K/Akt/eNOS pathway was observed, with increased p-Akt and p-eNOS expression.

Conclusions:

• κ-OR activation ameliorates vascular endothelial dysfunction in salt-sensitive hypertension.
• The protective effects are mediated through the PI3K/Akt/eNOS signaling pathway.
• κ-OR activation represents a promising therapeutic avenue for hypertension management.