Increased mechanosensitive currents in aortic endothelial cells from genetically hypertensive rats

Area of Science:

• Cardiovascular Physiology
• Endothelial Cell Biology
• Ion Channel Function

Background:

• Endothelial cells play a crucial role in regulating vascular tone and function.
• Mechanosensitive ion channels in endothelial cells are involved in sensing mechanical stimuli.
• Alterations in endothelial cell function are implicated in the pathogenesis of hypertension.

Purpose of the Study:

• To characterize and compare mechanosensitive whole-cell currents in rat aortic endothelial cells.
• To investigate differences in these currents between spontaneously hypertensive rats and normotensive controls.

Main Methods:

• Patch-clamp technique was used to measure whole-cell currents in response to hypotonic cell swelling.
• Pharmacological agents (gadolinium, charybdotoxin) and cytoskeletal disruptors (cytochalasin B, nocodazole) were employed.
• Experimental hypertension was induced in spontaneously hypertensive rats.

Main Results:

• Hypotonic cell swelling significantly increased outward-directed K+ currents in rat aortic endothelial cells.
• Stretch-activated cation channels and Ca(2+)-dependent K+ channels contributed to these currents.
• Disruption of actin filaments and microtubules attenuated the swelling-induced currents.
• Hypotonic swelling-induced whole-cell conductance was significantly higher in spontaneously hypertensive rats compared to controls.

Conclusions:

• Increased hypotonic swelling-induced currents in hypertensive rats suggest enhanced density or mechanosensitivity of stretch-activated ion channels.
• These findings indicate a potential alteration in endothelial mechanotransduction in experimental hypertension.
• This altered mechanotransduction may contribute to the development or maintenance of hypertension.