Contribution of Kv7 Channels to Natriuretic Peptide Mediated Vasodilation in Normal and Hypertensive Rats

Stott, Jennifer B.; Barrese, Vincenzo; Jepps, Thomas A.; Leighton, Emma; Greenwood, Iain A.

doi:10.1161/hypertensionaha.114.04373

Cited by 55 publications

(77 citation statements)

References 25 publications

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“…31) Marrachelli et al 26) found that the impaired ANP-induced relaxation in the renal artery of diabetic rabbits was at least partly due to the impaired participation of K ATP , K v , and K Ca channels. Recently, Stott et al 50) observed that the ANP-induced vasodilation was mediated by K v 7 channels in the rat aorta and renal artery, and suggested that the reduced ANP-induced vasodilation in such arteries of SHR was attributable to impaired K v 7 activity. In the present study, ANP-induced relaxation was altered by neither 4-AP (K v inhibitior) nor glibenclamide (K ATP inhibitor) in carotid arteries from both SHR and WKY.…”

Section: Discussionmentioning

confidence: 99%

“…Relaxation responses are shown as a percentage of the PE-induced pre-contraction. For the functional studies, individual concentration-response curves were analyzed using a nonlinear regression curve fitting relaxation-drug concentration relationships to determine E max (the maximal response generated by the relaxant drugs), pD 2 (a negative logarithm of EC 50 which is the concentration of the agonist producing 50% of E max ), and area under the curve (AUC), using Graph Pad Prism software (ver. 5.0 for Mac, San Diego, CA, U.S.A.).…”

Section: )mentioning

confidence: 99%

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Relaxation Induced by Atrial Natriuretic Peptide Is Impaired in Carotid but Not Renal Arteries from Spontaneously Hypertensive Rats Due to Reduced BK<sub>Ca</sub> Channel Activity

Matsumoto

Watanabe

Yamada

et al. 2015

Biological & Pharmaceutical Bulletin

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Atrial natriuretic peptide (ANP) plays an important role in vascular functions such as blood pressure regulation and relaxant activity. Individual vascular beds exhibit differences in vascular reactivity to various ligands, however, the difference in responsiveness to ANP between carotid and renal arteries and the molecular mechanisms of its vasorelaxant activity in a pathophysiological state, including hypertension, remain unclear. We therefore investigated this issue by exposing carotid and renal artery rings obtained from spontaneously hypertensive rats (SHR) to ANP. In the SHR artery (vs. control WKY artery), the ANP-induced relaxations were reduced in carotid artery but not renal artery. Acetylcholine-induced relaxations were reduced in both arteries in SHR (vs. WKY). Sodium nitroprusside-induced relaxation was similar in both arteries between the groups. In carotid arteries, the ANP-induced relaxation was not affected by endothelial denudation or by treatment with inhibitors of nitric oxide synthase, cyclooxygenase, the voltage-dependent potassium channel, or ATP-sensitive potassium channel in arteries from both SHR and WKY. In the carotid artery from WKY but not SHR, the ANP-induced relaxation was significantly reduced by inhibition of the large-conductance calcium-activated potassium channel (BK Ca ). The BK Ca activator-induced relaxation was reduced in the SHR artery (vs. WKY). These results suggest that ANP-induced relaxation is impaired in the carotid artery from SHR and this impairment may be at least in part due to the reduction of BK Ca activity rather than endothelial components.Key words atrial natriuretic peptide (ANP); carotid artery; potassium channel; relaxation; spontaneously hypertensive rat (SHR) Hypertension contributes markedly to global cardiovascular morbidity and mortality.1-3) Vascular dysfunction is a hallmark of hypertension and frequently leads to the development of atherosclerosis, stroke, and peripheral arterial disease.1,4) In vascular dysfunction, abnormalities of vascular smooth muscle cells and endothelial cells are key factors in the development of hypertension-associated vascular complications. 5-7)It has been shown that endogenous vasoactive peptides such as angiotensin II, endothelin-1, urotensin II, and natriuretic peptides play an important role in the regulation of vascular tone in (patho) physiological conditions. 8-11) Several reports suggested that the signalings of vasoactive peptides, including their production, metabolism, and affected vascular functions, are altered in arteries from hypertensive patients and animal models.6,10,12) Therefore, the manipulation of vasoactive peptide signaling is one of the most important strategies against the development of vascular dysfunction in hypertension.Atrial natriuretic peptide (ANP) has received particular attention since its effects on the cardiac function and blood pressure regulation have been reported through various mechanisms, including diuretic, natriuretic, and vasorelaxation. [13][14][15][16][17][18][19][20][2...

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Section: Discussionmentioning

confidence: 99%

Section: )mentioning

confidence: 99%

Relaxation Induced by Atrial Natriuretic Peptide Is Impaired in Carotid but Not Renal Arteries from Spontaneously Hypertensive Rats Due to Reduced BK<sub>Ca</sub> Channel Activity

Matsumoto

Watanabe

Yamada

et al. 2015

Biological & Pharmaceutical Bulletin

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“…Renal artery segments (∼2 mm) were mounted in a myograph (Danish Myo Technology) for isometric tension recording (13). The chambers contained physiological salt solution, maintained at 37°C and aerated with 95% O 2 /5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

“…There are five Kv7 isoforms (Kv7.1-Kv7.5) of which Kv7.1, Kv7.4, and Kv7.5 are consistently expressed within VSM, where the predominant molecular architecture is a Kv7.4/Kv7.5 heterotetramer (2,3). Activation of Kv7 channels produces relaxation of numerous arteries (4)(5)(6)(7)(8), whereas blockade of Kv7 channels results in contraction of vessels at rest (7,(9)(10)(11) or an inhibition of endogenously derived vasorelaxations (2,(11)(12)(13). In addition, molecular reduction of Kv7.4 reduces responses to various Gs-coupled vasodilators in a number of arteries (2,11).…”

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confidence: 99%

G-protein βγ subunits are positive regulators of Kv7.4 and native vascular Kv7 channel activity

Stott¹,

Povstyan²,

Carr³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Kv7.4 channels are a crucial determinant of arterial diameter both at rest and in response to endogenous vasodilators. However, nothing is known about the factors that ensure effective activity of these channels. We report that G-protein βγ subunits increase the amplitude and activation rate of whole-cell voltage-dependent K + currents sensitive to the Kv7 blocker linopirdine in HEK cells heterologously expressing Kv7.4, and in rat renal artery myocytes. In excised patch recordings, Gβγ subunits (2-250 ng /mL) enhanced the open probability of Kv7.4 channels without changing unitary conductance. Kv7 channel activity was also augmented by stimulation of G-protein-coupled receptors. Gallein, an inhibitor of Gβγ subunits, prevented these stimulatory effects. Moreover, gallein and two other structurally different Gβγ subunit inhibitors (GRK2i and a β-subunit antibody) abolished Kv7 channel currents in the absence of either Gβγ subunit enrichment or G-protein-coupled receptor stimulation. Proximity ligation assay revealed that Kv7.4 and Gβγ subunits colocalized in HEK cells and renal artery smooth muscle cells. Gallein disrupted this colocalization, contracted whole renal arteries to a similar degree as the Kv7 inhibitor linopirdine, and impaired isoproterenol-induced relaxations. Furthermore, mSIRK, which disassociates Gβγ subunits from α subunits without stimulating nucleotide exchange, relaxed precontracted arteries in a linopirdine-sensitive manner. These results reveal that Gβγ subunits are fundamental for Kv7.4 activation and crucial for vascular Kv7 channel activity, which has major consequences for the regulation of arterial tone.Kv7 channels | KCNQ genes | G-protein beta gamma subunits | electrophysiology | vascular biology

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“…The recent findings published in Stott et al 7 reveal that Kv7 channels are involved in mediating cyclic GMP (cGMP) dependent relaxations in the rat vasculature. The guanylate cyclase cGMP signaling pathway is a key vasodilator pathway involved in the regulation of vascular smooth muscle contractility.…”

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confidence: 99%

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

Stott

Greenwood²

2015

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Contribution of Kv7 Channels to Natriuretic Peptide Mediated Vasodilation in Normal and Hypertensive Rats

Cited by 55 publications

References 25 publications

Relaxation Induced by Atrial Natriuretic Peptide Is Impaired in Carotid but Not Renal Arteries from Spontaneously Hypertensive Rats Due to Reduced BK<sub>Ca</sub> Channel Activity

Relaxation Induced by Atrial Natriuretic Peptide Is Impaired in Carotid but Not Renal Arteries from Spontaneously Hypertensive Rats Due to Reduced BK<sub>Ca</sub> Channel Activity

G-protein βγ subunits are positive regulators of Kv7.4 and native vascular Kv7 channel activity

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

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