NO and K<sub>ATP</sub> channels underlie endotoxin‐induced smooth muscle hyperpolarization in rat mesenteric resistance arteries

Wu, Chang‐Chieh; Chen, S J; Garland, C J

doi:10.1038/sj.bjp.0705794

Cited by 19 publications

(10 citation statements)

References 33 publications

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“…A recent study looking at membrane potential in endothelial cells showed that responses induced by acetylcholine were even shorter in duration when ouabain was added, implicating a role for Na ϩ -K ϩ -ATPase in the maintenance of response (5). It has been reported that NO can cause hyperpolarization of vascular smooth muscle (12,38) through its direct actions on ATP-sensitive K ϩ channels (4,40). However, our data found only a small and statistically insignificantly different contribution of NO to hyperpolarization.…”

Section: Discussioncontrasting

confidence: 56%

Elucidation of the temporal relationship between endothelial-derived NO and EDHF in mesenteric vessels

Harrington¹,

Carrier²,

Gallagher³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Although the endothelium co-generates both nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), the relative contribution from each vasodilator is not clear. In studies where the endothelium is stimulated acutely, EDHF responses predominate in small arteries. However, the temporal relationship between endothelial-derived NO and EDHF over more prolonged periods is unclear but of major physiological importance. Here we have used a classical pharmacological approach to show that EDHF is released transiently compared with NO. Acetylcholine (3 ϫ 10 Ϫ6 mol/l) dilated second-and/or thirdorder mesenteric arteries for prolonged periods of up to 1 h, an effect that was reversed fully and immediately by the subsequent addition of L-NAME (10 Ϫ3 mol/l) but not TRAM-34 (10 Ϫ6 mol/l) plus apamin (5 ϫ 10 Ϫ7 mol/l). When vessels were pretreated with L-NAME, acetylcholine induced relatively transient dilator responses (declining over ϳ5 min), and vessels were sensitive to TRAM-34 plus apamin. When measured in parallel, the dilator effects of acetylcholine outlasted the smooth muscle hyperpolarization. However, in the presence of L-NAME, vasodilatation and hyperpolarization followed an identical time course. In vessels from NOSIII Ϫ/Ϫ mice, acetylcholine induced small but detectable dilator responses that were transient in duration and blocked by TRAM-34 plus apamin. EDHF responses in these mouse arteries were inhibited by an intracellular calcium blocker, TMB-8, and the phospholipase A 2 inhibitor AACOCF3, suggesting a role for lipid metabolites. These data show for the first time that EDHF is released transiently, whereas endothelial-derived NO is released in a sustained manner.arteries; vasodilation; mediators; hyperpolarization; nitric oxide; endothelium-derived hyperpolarizing factor THE ENDOTHELIUM-DERIVED relaxing factor, described in 1980 by Furchgott and Zawadozki (18), is now known to be nitric oxide (NO) (22, 23), formed from the amino acid L-arginine (32). In 1988, reports emerged of a distinct factor released by the endothelium that relaxed blood vessels via a process of hyperpolarization (endothelium-derived hyperpolarizing factor; EDHF) (2,3,15). Since this time, EDHF biology has developed at a rapid pace (9). However, there is still considerable debate about the identity of EDHF. Potential candidates include CYP450 metabolites (17), K ϩ (16), hydrogen peroxide (26), and K ϩ and/or electrical communications through gap junctions (39) and possibly C-type natriuretic peptide (CNP) (13).Much of the evidence supporting a role for EDHF in endothelium-dependent dilation has been derived pharmacologically, for example, by removing other dilatory pathways (NO and prostacyclin), removing the endothelium, removing the ability to hyperpolarize (with high [K ϩ ]), or blocking K ϩ channels with agents such as TRAM-34 plus apamin. Usually, experiments are conducted where the vessels are stimulated acutely and the responses monitored for short periods of time (seconds or minutes). The temporal nature of EDHF is...

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Section: Discussioncontrasting

confidence: 56%

Elucidation of the temporal relationship between endothelial-derived NO and EDHF in mesenteric vessels

Harrington¹,

Carrier²,

Gallagher³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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“…The endothelium-free rings were prepared by gently rubbing with a sanded polyethylene tube and confirmed with vasodilation response to acetylcholine. The isolated mesenteric arteries were transferred to icecold Krebs solution containing NaCl 118.0, NaHCO 3 25.0, KCl 3.6, MgSO4 1.2, KH2PO4 1.2, glucose 11.0, CaCl2 2.5 in mM (42). A ring segment 2 mm in length was mounted on a force electricity transducer (model FT-302; iWorx/CBSciences, Dover, NH) in a tissue bath with 5 ml Krebs solution.…”

Section: Methodsmentioning

confidence: 99%

Arginine vasopressin inhibits Kir6.1/SUR2B channel and constricts the mesenteric artery via V1a receptor and protein kinase C

Shi¹,

Cui²,

Shi³

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

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Kir6.1/SUR2B channel is the major isoform of K(ATP) channels in the vascular smooth muscle. Genetic disruption of either subunit leads to dysregulation of vascular tone and regional blood flows. To test the hypothesis that the Kir6.1/SUR2B channel is a target molecule of arginine vasopressin (AVP), we performed studies on the cloned Kir6.1/SUR2B channel and cell-endogenous K(ATP) channel in rat mesenteric arteries. The Kir6.1/SUR2B channel was expressed together with V1a receptor in the HEK-293 cell line. Whole cell currents of the transfected HEK cells were activated by K(ATP) channel opener pinacidil and inhibited by K(ATP) channel inhibitor glibenclamide. AVP produced a concentration-dependent inhibition of the pinacidil-activated currents with IC(50) 2.0 nM. The current inhibition was mediated by a suppression of the open-state probability without effect on single-channel conductance. An exposure to 100 nM PMA, a potent PKC activator, inhibited the pinacidil-activated currents, and abolished the channel inhibition by AVP. Such an effect was not seen with inactive phorbol ester. A pretreatment of the cells with selective PKC blocker significantly diminished the inhibitory effect of AVP. In acutely dissociated vascular smooth myocytes, AVP strongly inhibited the cell-endogenous K(ATP) channel. In isolated mesenteric artery rings, AVP produced concentration-dependent vasoconstrictions with EC(50) 6.5 nM. At the maximum effect, pinacidil completely relaxed vasoconstriction in the continuing exposure to AVP. The magnitude of the AVP-induced vasoconstriction was significantly reduced by calphostin-C. These results therefore indicate that the Kir6.1/SUR2B channel is a target molecule of AVP, and the channel inhibition involves G(q)-coupled V1a receptor and PKC.

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“…Nitric oxide was also shown to hyperpolarize SMCs in rabbit mesenteric arteries via a mechanism that involves cGMP and activation of K ATP channels (1040). Hyperpolarization induced by NO was also shown to involve K ATP channels in mesenteric SMCs (1547). K ATP channels have also been implicated in vasodilation induced by NO in several other systems (57, 581).…”

Section: Katp 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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NO and K_ATP channels underlie endotoxin‐induced smooth muscle hyperpolarization in rat mesenteric resistance arteries

Cited by 19 publications

References 33 publications

Elucidation of the temporal relationship between endothelial-derived NO and EDHF in mesenteric vessels

Elucidation of the temporal relationship between endothelial-derived NO and EDHF in mesenteric vessels

Arginine vasopressin inhibits Kir6.1/SUR2B channel and constricts the mesenteric artery via V1a receptor and protein kinase C

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

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NO and KATP channels underlie endotoxin‐induced smooth muscle hyperpolarization in rat mesenteric resistance arteries

Cited by 19 publications

References 33 publications

Elucidation of the temporal relationship between endothelial-derived NO and EDHF in mesenteric vessels

Elucidation of the temporal relationship between endothelial-derived NO and EDHF in mesenteric vessels

Arginine vasopressin inhibits Kir6.1/SUR2B channel and constricts the mesenteric artery via V1a receptor and protein kinase C

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

Contact Info

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About

NO and K_ATP channels underlie endotoxin‐induced smooth muscle hyperpolarization in rat mesenteric resistance arteries