July 15, 2002Open Access
Episodic coronary artery vasospasm and hypertension develop in the absence of Sur2 KATP channels
Key Result
Sur2 gene-targeted mice exhibited significantly elevated resting blood pressures, sudden death, and transient coronary artery vasospasm that was reduced by a calcium channel antagonist.
Structured PICO
P
Population
Sur2 gene-targeted mice (Sur2(-/-)) used as an animal model to study the role of K(ATP) channels in vascular smooth muscle.
E
Exposure
Calcium channel antagonist
O
Outcome
Resting blood pressure, sudden death, and coronary artery vasospasm episodes
The SUR2 K(ATP) channel is a critical regulator of episodic vasomotor activity, and its absence in mice provides a model for Prinzmetal variant angina.
Abstract
K(ATP) channels couple the intracellular energy state to membrane excitability and regulate a wide array of biologic activities. K(ATP) channels contain a pore-forming inwardly rectifying potassium channel and a sulfonylurea receptor regulatory subunit (SUR1 or SUR2). To clarify the role of K(ATP) channels in vascular smooth muscle, we studied Sur2 gene-targeted mice (Sur2(-/-)) and found significantly elevated resting blood pressures and sudden death. Using in vivo monitoring, we detected transient, repeated episodes of coronary artery vasospasm in Sur2(-/-) mice. Focal narrowings in the coronary arteries were present in Sur2(-/-) mice consistent with vascular spasm. We treated Sur2(-/-) mice with a calcium channel antagonist and successfully reduced vasospastic episodes. The intermittent coronary artery vasospasm seen in Sur2(-/-) mice provides a model for the human disorder Prinzmetal variant angina and demonstrates that the SUR2 K(ATP) channel is a critical regulator of episodic vasomotor activity.