Block of Inward Rectifying K
            <sup>+</sup>
            Channels (K
            <sub>IR</sub>
            ) Inhibits Bradykinin-Induced Vasodilatation in Human Forearm Resistance Vasculature

Dwivedi, Rahul; Saha, S. K.; Chowienczyk, Phil; Ritter, James M.

doi:10.1161/01.atv.0000152610.40086.31

Cited by 20 publications

(27 citation statements)

References 31 publications

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“…These channels also participate in propagation of hyperpolarizing signals along arterioles (689, 1204, 1313). Inward rectifier K + channels also have been proposed to contribute to bradykinin-induced dilation in human forearm (356). C-type natriuretic peptide, a putative endothelium-derived hyperpolarizing factor (EDHF) may act, in part, by activation of K IR channels (222).…”

Section: Kir Channelsmentioning

confidence: 99%

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Tykocki

Boerman

Jackson

2017

Comprehensive Physiology

282

347

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Vascular tone of resistance arteries and arterioles determines peripheral vascular resistance, contributing to the regulation of blood pressure and blood flow to, and within the body’s tissues and organs. Ion channels in the plasma membrane and endoplasmic reticulum of vascular smooth muscle cells (SMCs) in these blood vessels importantly contribute to the regulation of intracellular Ca2+ concentration, the primary determinant of SMC contractile activity and vascular tone. Ion channels provide the main source of activator Ca2+ that determines vascular tone, and strongly contribute to setting and regulating membrane potential, which, in turn, regulates the open-state-probability of voltage gated Ca2+ channels (VGCCs), the primary source of Ca2+ in resistance artery and arteriolar SMCs. Ion channel function is also modulated by vasoconstrictors and vasodilators, contributing to all aspects of the regulation of vascular tone. This review will focus on the physiology of VGCCs, voltage-gated K+ (KV) channels, large-conductance Ca2+-activated K+ (BKCa) channels, strong-inward-rectifier K+ (KIR) channels, ATP-sensitive K+ (KATP) channels, ryanodine receptors (RyRs), inositol 1,4,5-trisphosphate receptors (IP3Rs), and a variety of transient receptor potential (TRP) channels that contribute to pressure-induced myogenic tone in resistance arteries and arterioles, the modulation of the function of these ion channels by vasoconstrictors and vasodilators, their role in the functional regulation of tissue blood flow and their dysfunction in diseases such as hypertension, obesity, and diabetes.

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Section: Kir Channelsmentioning

confidence: 99%

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Tykocki

Boerman

Jackson

2017

Comprehensive Physiology

282

347

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“…03125, Sigma, St. Louis, MO) and BaCl2 [10% (wt/vol) BDH-3238, EMD Chemicals, Gibbstown, NJ] were administered intra-arterially as previously described (17). Ouabain was infused at 2.7 nmol/min for 15 min as a loading dose to inhibit Na ϩ -K ϩ -ATPase, and BaCl2, was infused at 0.45 mol·dl forearm volume Ϫ1 ·min Ϫ1 with a minimum dose of 4 mol/min to a maximum dose of 5 mol/min for 3 min as a loading dose to inhibit K IR channels (9,17,21,27,37). This dose of BaCl2 has been adjusted to forearm volume compared with our previous study (17) to maximize efficacy while still remaining within doses safe for human administration and specific for KIR channels (21,36).…”

Section: Vasoactive Drug Infusionsmentioning

confidence: 99%

Mechanisms of rapid vasodilation after a brief contraction in human skeletal muscle

Crecelius

Kirby

Luckasen

et al. 2013

American Journal of Physiology-Heart and Circulatory Physiology

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Crecelius AR, Kirby BS, Luckasen GJ, Larson DG, Dinenno FA. Mechanisms of rapid vasodilation after a brief contraction in human skeletal muscle. Am J Physiol Heart Circ Physiol 305: H29-H40, 2013. First published May 3, 2013 doi:10.1152/ajpheart.00298.2013.-A monophasic increase in skeletal muscle blood flow is observed after a brief single forearm contraction in humans, yet the underlying vascular signaling pathways remain largely undetermined. Evidence from experimental animals indicates an obligatory role of vasodilation via K ϩ -mediated smooth muscle hyperpolarization, and human data suggest little to no independent role for nitric oxide (NO) or vasodilating prostaglandins (PGs). We tested the hypothesis that K ϩ -mediated vascular hyperpolarization underlies the rapid vasodilation in humans and that combined inhibition of NO and PGs would have a minimal effect on this response. We measured forearm blood flow (Doppler ultrasound) and calculated vascular conductance 10 s before and for 30 s after a single 1-s dynamic forearm contraction at 10%, 20%, and 40% maximum voluntary contraction in 16 young adults. To inhibit K ϩ -mediated vasodilation, BaCl2 and ouabain were infused intraarterially to inhibit inwardly rectifying K ϩ channels and Na ϩ -K ϩ -ATPase, respectively. Combined enzymatic inhibition of NO and PG synthesis occurred via N G -monomethyl-L-arginine (L-NMMA; NO synthase) and ketorolac (cyclooxygenase), respectively. In protocol 1 (n ϭ 8), BaCl 2 ϩ ouabain reduced peak vasodilation (range: 30 -45%, P Ͻ 0.05) and total postcontraction vasodilation (area under the curve, ϳ55-75% from control) at all intensities. Contrary to our hypothesis, L-NMMA ϩ ketorolac had a further impact (peak: ϳ60% and area under the curve: ϳ80% from control). In protocol 2 (n ϭ 8), the order of inhibitors was reversed, and the findings were remarkably similar. We conclude that K ϩ -mediated hyperpolarization and NO and PGs, in combination, significantly contribute to contraction-induced rapid vasodilation and that inhibition of these signaling pathways nearly abolishes this phenomenon in humans.hyperemia; exercise; potassium THE REGULATION of skeletal muscle hyperemia during muscle contractions is complex and involves a variety of signals that control both the arteriovenous perfusion pressure gradient and arteriolar caliber (10, 13). In an attempt to isolate the local mechanisms underlying exercise hyperemia, early experiments used a single brief muscle contraction to allow for contractioninduced hyperemia without the continuous interruption of the blood flow response or further stimulus for hyperemia, as occurs with repeated contractions (16). In this regard, the single contraction model can serve as a tool to examine feedforward mechanisms of hyperemia that are largely independent of changes in tissue oxidative metabolism (48). The typical response is characterized by an intensity-dependent, rapid, monophasic increase in blood flow that occurs immediately (within one cardiac cycle) after contraction, achieves full magni...

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“…22 The brachial artery of the nondominant arm was cannulated with a 27-gauge needle under local anesthesia (0.1% lignocaine) and used for drug infusions. All drugs were dissolved in 0.9% saline.…”

Section: Assessment Of Resistance Vessel Endothelial Function: Forearmentioning

confidence: 99%

Vascular Dysfunction and Reduced Circulating Endothelial Progenitor Cells in Young Healthy UK South Asian Men

Murphy

Kanaganayagam

Jiang

et al. 2007

ATVB

135

108

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Block of Inward Rectifying K ⁺ Channels (K _IR ) Inhibits Bradykinin-Induced Vasodilatation in Human Forearm Resistance Vasculature

Cited by 20 publications

References 31 publications

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Mechanisms of rapid vasodilation after a brief contraction in human skeletal muscle

Vascular Dysfunction and Reduced Circulating Endothelial Progenitor Cells in Young Healthy UK South Asian Men

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Block of Inward Rectifying K + Channels (K IR ) Inhibits Bradykinin-Induced Vasodilatation in Human Forearm Resistance Vasculature

Cited by 20 publications

References 31 publications

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Smooth Muscle Ion Channels and Regulation of Vascular Tone in Resistance Arteries and Arterioles

Mechanisms of rapid vasodilation after a brief contraction in human skeletal muscle

Vascular Dysfunction and Reduced Circulating Endothelial Progenitor Cells in Young Healthy UK South Asian Men

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Product

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About

Block of Inward Rectifying K ⁺ Channels (K _IR ) Inhibits Bradykinin-Induced Vasodilatation in Human Forearm Resistance Vasculature