Complex role of Kv7 channels in cGMP and cAMP-mediated relaxations

Rhus coriaria L. (Sumac) Evokes Endothelium-Dependent Vasorelaxation of Rat Aorta: Involvement of the cAMP and cGMP Pathways

“…Voltage-dependent potassium channels have not been examined in the present study, but it is feasible that RCE-mediated relaxation is modulated by both cAMP and cGMP pathways via stimulation of K V 7.4/7.5 channels ( Stott and Greenwood, 2015 ). Moreover, EPAC-dependent arterial relaxation can occur in part via activation of K V 7.4 channels ( Stott and Greenwood, 2015 ). Importantly, EPAC is also known to raise the activity of BK Ca channels leading to VSM relaxation ( Roberts et al, 2013 ).…”

Perivascular adipose tissue and the dynamic regulation of Kv7 and Kir channels: Implications for resistant hypertension

“…Notably, this K v 7‐channel isoform underlies impaired beta‐adrenoceptor–mediated relaxation of renal arteries in hypertension and contributes in multimeric channel complexes with KCNQ5 to calcitonin gene‐related peptide‐induced cerebral reactivity . Vascular K v 7 channels are regulated by natriuretic peptide and other vasodilatory receptor agonists (for review). K v 7 channels (in particular K v 7.1 and K v 7.5) are highly expressed in left coronary arteries of rats, and their down‐regulation by diabetes critically determines the sensitivity (forskolin and hypoxia) to key regulators of coronary tone .…”

“…Down‐regulation of K v 7.4 has been implicated in primary and angiotensin II infusion‐induced hypertension . As K v 7 channels also contribute to natriuretic peptide‐mediated vasodilation in normal and hypertensive rats via the cGMP‐dependent signaling pathway, the major conclusion to be drawn from K v 7 channels is they play central roles in both cGMP‐ and cAMP‐mediated relaxations . However, the situation in vivo appears more complex as G protein βγ subunits by themselves can enhance the open probability of K v 7.4 channels …”

The Kv7 Channel and Cardiovascular Risk Factors

“…The β-adrenergic cAMP-mediated vasodilatory pathway is diminished in the vasculature of SHR (Figure 2 ) ( 21 , 29 ). Isoprenaline-induced vasodilation of rat renal arteries was reduced in the presence of the pharmacological Kv7.4 blocker linopirdine, as well as in experiments with siRNA-induced knock down targeting Kv7.4 in isolated vessels ( 21 , 52 ). The ability of isoprenaline to enhance Kv7 channel activity is diminished in SHR, possibly due to the reduced expression or function of Kv7.4.…”

“…Like cAMP, the cyclic GMP (cGMP)-mediated signaling pathway plays a central role in the control of vascular tone ( 29 , 52 ). Activation of soluble guanylate cyclase by liberated nitric oxide is one out of two mechanisms that increase cGMP in VSMC.…”