TY - JOUR

T1 - Contribution of Kv7 channels to natriuretic peptide mediated vasodilation in normal and hypertensive rats

AU - Stott, Jennifer B

AU - Barrese, Vincenzo

AU - Jepps, Thomas Andrew

AU - Leighton, Emma V

AU - Greenwood, Iain A

N1 - © 2014 American Heart Association, Inc.

PY - 2015/3

Y1 - 2015/3

N2 - The Kv7 family of voltage-gated potassium channels are expressed within the vasculature where they are key regulators of vascular tone and mediate cAMP-linked endogenous vasodilator responses, a pathway that is compromised in hypertension. However, the role of Kv7 channels in non-cAMP-linked vasodilator pathways has not been investigated. Natriuretic peptides are potent vasodilators, which operate primarily through the activation of a cGMP-dependent signaling pathway. This study investigated the putative role of Kv7 channels in natriuretic peptide-dependent relaxations in the vasculature of normal and hypertensive animals. Relaxant responses of rat aorta to both atrial and C-type natriuretic peptides and the nitric oxide donor sodium nitroprusside were impaired by the Kv7 blocker linopirdine (10 μmol/L) but not by the Kv7.1-specific blocker HMR1556 (10 μmol/L) and other K(+) channel blockers. In contrast, only the atrial natriuretic peptide response was sensitive to linopirdine in the renal artery. These Kv7-mediated responses were attenuated in arteries from hypertensive rats. Quantitative polymerase chain reaction showed that A- and B-type natriuretic peptide receptors were expressed at high levels in the aorta and renal artery from normal and spontaneously hypertensive rats. This study provides the first evidence that natriuretic peptide responses are impaired in hypertension and that recruitment of Kv7 channels is a key component of natriuretic peptide-dependent vasodilations.

AB - The Kv7 family of voltage-gated potassium channels are expressed within the vasculature where they are key regulators of vascular tone and mediate cAMP-linked endogenous vasodilator responses, a pathway that is compromised in hypertension. However, the role of Kv7 channels in non-cAMP-linked vasodilator pathways has not been investigated. Natriuretic peptides are potent vasodilators, which operate primarily through the activation of a cGMP-dependent signaling pathway. This study investigated the putative role of Kv7 channels in natriuretic peptide-dependent relaxations in the vasculature of normal and hypertensive animals. Relaxant responses of rat aorta to both atrial and C-type natriuretic peptides and the nitric oxide donor sodium nitroprusside were impaired by the Kv7 blocker linopirdine (10 μmol/L) but not by the Kv7.1-specific blocker HMR1556 (10 μmol/L) and other K(+) channel blockers. In contrast, only the atrial natriuretic peptide response was sensitive to linopirdine in the renal artery. These Kv7-mediated responses were attenuated in arteries from hypertensive rats. Quantitative polymerase chain reaction showed that A- and B-type natriuretic peptide receptors were expressed at high levels in the aorta and renal artery from normal and spontaneously hypertensive rats. This study provides the first evidence that natriuretic peptide responses are impaired in hypertension and that recruitment of Kv7 channels is a key component of natriuretic peptide-dependent vasodilations.

KW - Animals

KW - Aorta

KW - Cyclic GMP

KW - Disease Models, Animal

KW - Hypertension

KW - KCNQ Potassium Channels

KW - Muscle, Smooth, Vascular

KW - Natriuretic Peptides

KW - Nitroprusside

KW - Potassium Channel Blockers

KW - Rats

KW - Rats, Inbred SHR

KW - Rats, Wistar

KW - Renal Artery

KW - Signal Transduction

KW - Vasodilation

U2 - 10.1161/HYPERTENSIONAHA.114.04373

DO - 10.1161/HYPERTENSIONAHA.114.04373

M3 - Journal article

C2 - 25547342

VL - 65

SP - 676

EP - 682

JO - Hypertension

JF - Hypertension

SN - 0194-911X

IS - 3

ER -