Effects of Obesity on Vascular Potassium Channels

Abstract

This review is focused on the effects of obesity on function and expression of potassium (K) channels in the vasculature. Five families of K channels have been identified in the vascular wall, calcium-activated K (KCa) channels, inward-rectifier K (KIR) channels, ATP-sensitive K (KATP) channels, voltage-gated K (KV) channels and two-pore domain K (K2P) channels. In endothelial cells (EC) and vascular smooth muscle cells (VSMC) opening of K channels leads to hyperpolarisation followed by vasodilatation. In some vascular beds of animal models of obesity, vasodilatation mediated by KCa3.1 and KCa2.3 channels has been reported to remain unaltered or even increased, whereas vasodilatation involving KCa1.1 channel has consistently been reported to be impaired. Changes in expression and function of KIR and KATP channels have also been associated with impaired vasodilatation in animal models of obesity, and therefore activation of these channels may improve endothelial function and reduce the risk of major cardiovascular events. Expression of KV7.x channels is downregulated in small arteries from hypertensive animals and it would be interesting to assess whether these channels contribute to development of hypertension in obese patients. However, the role of KV7.x and K2P channels in regulation of blood pressure remains unexplored compared to other K channels. In conclusion, obesity and metabolic syndrome alter expression, function and sensitivity of vascular K channel subtypes causing smooth muscle dysfunction and probably endothelial dysfunction which makes these patients particularly prone to premature cardiovascular disease. Modulation of K channel activity by use of openers of e.g. KCa and KATP channels may also be attractive to counteract vascular dysfunction observed in obesity.

Mechanisms underlying the vasorelaxation of human internal mammary artery induced by (-)-epicatechin

“…They are involved in a wide range of physiological processes, such as control of vascular tone and protection of cardiac cells against ischemic injuries (Martin et al, 2013). Changes in expression and function of K ATP channels have also been associated with impaired vasodilatation (Climent et al, 2014). Therefore, the activation of these channels may reduce the risk of the major cardiovascular events.…”

Comparisons between perivascular adipose tissue and the endothelium in their modulation of vascular tone

“…Various potassium channels (such as K Ca , K ir and K V ) have been implicated in the endothelial dysfunction observed in obesity and hypertension (reviewed by (Climent et al, ). The diminished anti‐contractile effect of PVAT observed in hypertension can be restored using KCNQ channel openers in rat Gracilis muscle arteries from spontaneously hypertensive rats, suggesting that a dysfunction in K + channels activation mediates the altered PVAT regulation of vascular tone (Zavaritskaya et al, ).…”

Decreased EDHF‐mediated relaxation is a major mechanism in endothelial dysfunction in resistance arteries in aged mice on prolonged high‐fat sucrose diet

“…; Climent et al. ). When small mesenteric arteries were treated with the NO synthase blocker L‐NAME and indomethacin, the residual EDH response tended to be lower after four months of HFS diet, but this did not reach statistical significance compared with mice given a normal diet.…”