AMP‐activated Protein Kinase is Necessary for Cardiorespiratory Adjustments during Hypoxia

Abstract

The AMP‐activated protein kinase (AMPK) has been proposed to underpin appropriate cardiorespiratory adjustments during hypoxia (Evans et al., 2006), and has been identified as a mediator of hypoxic pulmonary vasoconstriction (HPV) (Evans et al., 2005). Our objective was to assess by non‐invasive Echo Doppler ultrasound, the effect(s) on HPV of deleting LKB1, CAMKK‐β or the AMPKα1 & α2 catalytic subunits. Our preliminary investigations on wild type and transgenic mice suggest that the LKB1‐AMPK signalling pathway, but not CAMKK‐β, are required for HPV. Moreover, deletion of AMPK catalytic subunit(s) blocked hypoxia‐induced inhibition of voltage‐gated potassium currents (Kv) in acutely isolated pulmonary arterial smooth muscle cells. Therefore, AMPK underpins the regulation of pulmonary vascular responses to hypoxia at the molecular, cellular and system level.Evans et al. (2005). J. Biol Chem., 280, 41505‐41511.Evans (2006). J. Physiol., 574, 113‐123.