Endothelium-dependent relaxations in the aorta from K(2p)6.1 knockout mice

Area of Science:

• Cardiovascular Physiology
• Ion Channel Function
• Vascular Biology

Background:

• K2P6.1 (TWIK-2) is a two-pore domain potassium channel crucial for cardiovascular regulation.
• High expression of K2P6.1 in vascular smooth muscle and endothelium suggests a role in vascular tone.
• K2P6.1 knockout mice exhibit hypertension and enhanced vascular contractility.

Purpose of the Study:

• To investigate the role of endothelial K2P6.1 in vascular dysfunction of K2P6.1 knockout mice.
• To test the hypothesis that K2P6.1 knockout mice have impaired endothelium-dependent relaxations.

Main Methods:

• Utilized K2P6.1 knockout (K2P6.1(-/-)) and wild-type (K2P6.1(+/+)) mice (8-12 wk and 20-24 wk).
• Assessed hypertension via blood pressure measurements.
• Evaluated endothelium-dependent relaxations of the thoracic aorta using isometric myography.
• Administered acetylcholine (ACh), indomethacin, ATP, A23187, and nitro-L-arginine methyl ester (L-NAME).

Main Results:

• K2P6.1(-/-) mice were significantly more hypertensive than WT littermates.
• Maximal ACh-dependent relaxations were significantly increased in aortas from K2P6.1(-/-) mice compared to WT.
• Indomethacin treatment normalized ACh-dependent relaxations in WT mice to knockout levels.
• Enhanced relaxations were observed with ATP and A23187 in mature K2P6.1(-/-) mice.
• ACh-mediated contraction was attenuated in K2P6.1(-/-) aorta under L-NAME conditions.

Conclusions:

• Hypertensive K2P6.1 knockout mice display enhanced endothelium-dependent aortic relaxations.
• The enhanced relaxation is attributed to the suppression of an indomethacin-sensitive constrictor pathway.
• Endothelial K2P6.1 plays a significant role in regulating vascular tone and blood pressure.