Compromised vascular endothelial cell SK(Ca) activity: a fundamental aspect of hypertension?
Smooth muscle hyperpolarization originating in the endothelium and commonly referred to as the EDHF (endothelium-derived hyperpolarizing factor) response provides a very significant drive to vasodilatation particularly in small resistance arteries. Together with other endothelium-dependent dilator pathways 'EDHF' hyperpolarization is compromised by cardiovascular disease, including hypertension. However, although attenuated vascular hyperpolarization has been described in animal models of hypertension, the underlying mechanisms are not fully understood. In the current issue of the British Journal of Pharmacology, Weston et al. combine classic pharmacological approaches with electrophysiological and molecular techniques to suggest that attenuated endothelium-dependent hyperpolarization (and as a consequence vasodilatation) reflects major disruption of pathways associated with the activation of endothelial small conductance Ca(2+)-activated K-channels (SK(Ca)) in mesenteric arteries from spontaneously hypertensive rats. In addition to reductions in SK(Ca) and K(IR) proteins, changes in caveolin-1 isomers were also detected, possibly indicating channel realignment within plasmalemmal structures.
Garland
Christopher J
CJ
Department of Pharmacology, University of Oxford, Oxford, UK. christopher.garland@pharm.ox.ac.uk
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001685:Biological Factors / Q000502:physiology; D015536:Down-Regulation / Q000502:physiology*; D006973:Hypertension / Q000188:drug therapy / Q000201:enzymology / Q000503:physiopathology*; D021962:Membrane Microdomains / Q000502:physiology; D008564:Membrane Potentials / Q000187:drug effects; D049990:Membrane Transport Modulators / Q000494:pharmacology; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology; D024661:Potassium Channels, Inwardly Rectifying / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D051640:Small-Conductance Calcium-Activated Potassium Channels / Q000819:agonists / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D000959:Antihypertensive Agents; D001685:Biological Factors; D049990:Membrane Transport Modulators; D024661:Potassium Channels, Inwardly Rectifying; D051640:Small-Conductance Calcium-Activated Potassium Channels; C067410:endothelium-dependent hyperpolarization factor