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Endothelium‐dependent hyperpolarization: age, gender and blood pressure, do they matter?
Author(s) -
Leung S. W. S.,
Vanhoutte P. M.
Publication year - 2017
Publication title -
acta physiologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.591
H-Index - 116
eISSN - 1748-1716
pISSN - 1748-1708
DOI - 10.1111/apha.12628
Subject(s) - vasodilation , prostacyclin , endocrinology , endothelium , nitric oxide , medicine , hyperpolarization (physics) , endothelium derived hyperpolarizing factor , endothelial dysfunction , chemistry , microbiology and biotechnology , biology , charybdotoxin , organic chemistry , nuclear magnetic resonance spectroscopy
Under physiological conditions, the endothelium generates vasodilator signals [prostacyclin, nitric oxide NO and endothelium‐dependent hyperpolarization ( EDH )], for the regulation of vascular tone. The relative importance of these two signals depends on the diameter of the blood vessels: as the diameter of the arteries decreases, the contribution of EDH to the regulation of vascular tone increases. The mechanism involved in EDH varies with species and blood vessel types; nevertheless, activation of endothelial intermediate‐ and small‐conductance calcium‐activated potassium channels ( IK C a and SK C a , respectively) is characteristic of the EDH pathway. IK C a ‐ and SK C a ‐mediated EDH are reduced with endothelial dysfunction, which develops with ageing and hypertension, and is less pronounced in female than in age‐matched male until after menopause. Impaired EDH ‐mediated relaxation is related to a reduced involvement of SK C a , so that the response becomes more dependent on IK C a . The latter depends on the activation of adenosine monophosphate‐activated protein kinase ( AMPK ) and silent information regulator T1 ( SIRT 1), proteins associated with the process of cellular senescence and vascular signalling in response to the female hormone. An understanding of the role of AMPK and/or SIRT 1 in EDH ‐like responses may help identifying effective pharmacological strategies to prevent the development of vascular complications of different aetiologies.