scholarly journals Endothelium-dependent responses in human isolated thyroid arteries from donors

2004 ◽  
Vol 181 (3) ◽  
pp. 379-384 ◽  
Author(s):  
B Torondel ◽  
JM Vila ◽  
G Segarra ◽  
P Lluch ◽  
P Medina ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Dominant Role ◽  
Human Thyroid ◽  
K Channel ◽  
Organ Donors ◽  
Inhibitory Effects ◽  
K Channels ◽  
High K ◽  
Inwardly Rectifying ◽  
Endothelium Dependent Relaxation

The functional properties of the endothelium of human thyroid arteries remain unexplored. We investigated the intervention of nitric oxide (NO), prostacyclin (PGI(2)) and endothelium-derived hyperpolarizing factor (EDHF) in the responses to acetylcholine and noradrenaline in isolated thyroid arteries obtained from multi-organ donors. Artery rings were suspended in organ baths for isometric recording of tension. The contribution of NO, PGI(2) and EDHF to endothelium-dependent relaxation was determined by the inhibitory effects of N(G)-monomethyl-L-arginine (L-NMMA), indomethacin, and K(+) channel inhibitors respectively. Acetylcholine induced concentration-dependent relaxation; this effect was not modified by indomethacin and was only partly reduced by L-NMMA, but was abolished in endothelium-denuded rings. The relaxation resistant to indomethacin and L-NMMA was abolished by using either apamin combined with charybdotoxin, ouabain plus barium, or a high-K(+) solution. Noradrenaline induced concentration-dependent contractions which were of greater magnitude in arteries denuded of endothelium or in the presence of L-NMMA.In conclusion, the results indicate that in human thyroid arteries the endothelium significantly modulates responses to acetylcholine and noradrenaline through the release of NO and EDHF. EDHF plays a dominant role in acetylcholine-induced relaxation through activation of Ca(2+)-activated K(+) channels, inwardly rectifying K(+) channels and Na(+)-K(+)-ATPase.

Docosahexaenoic Acid-Induced Vasorelaxation in Hypertensive Rats: Mechanisms of Action

2000 ◽  
Vol 2 (2) ◽  
pp. 85-95 ◽  
Author(s):  
Mary B. Engler ◽  
Marguerite M. Engler
Keyword(s):  
Nitric Oxide ◽  
Inhibitory Effect ◽  
Significant Inhibition ◽  
Isometric Tension ◽  
K Channel ◽  
Omega 3 ◽  
Hypertensive Rats ◽  
Blood Pressure Lowering Effect ◽  
K Channels ◽  
High K

The authors investigated the vasorelaxant properties of the omega-3 fatty acid, docosahexaenoic (DHA, 22:6n-3), and the possible involvement of endothelium-derived nitric oxide, prostanoids, opening of K+ channels, and/or modulation of calcium-mediated events. Isolated aorta from male spontaneously hypertensive rats (SHR) (age 16-17 weeks) were used to measure isometric tension. DHA-induced (1-100 mol/l) relaxation was examined following contraction to norepinephrine (NE) (10– 6 mol/l) or high-K+ (80 mmol/l) solution in the presence and absence of various inhibitors and calcium-containing solution. DHA acid induced a significant vasorelaxant effect in both NE and high-K+-induced contracted SHR aortic rings, although DHA relaxations were greater in high-K+-induced contracted rings. In the absence of extracellular calcium, DHA (5-30 mol/l) inhibited the initial phasic and sustained components of NE-induced contraction under different conditions. Inhibition of nitric oxide synthesis by N•-nitro-L-arginine methyl ester hydrochloride (100 mol/l) had no effect on DHA relaxations; however, indomethacin or nifedipine caused significant inhibition at• 30 mol/l DHA. The K+ channel blocker, glibenclamide, but not tetraethyl-ammonium, also had an inhibitory effect on DHA-induced relaxation. These results indicate that DHA’s vasorelaxant actions in SHR aorta are independent of endothelium-derived nitric oxide; however, at DHA concentrations• 30 mol/l, vasodilatory prostanoids that activate AT Psensitive K+ channels (KATP) may be involved. At lower concentrations, DHA-induced relaxation appears to be attributed to modulation of intracellular Ca2+release and L-type Ca2+channels in vascular smooth muscle cells. The vasorelaxant properties of DHA may contribute, in part, to the blood pressure–lowering effect of dietary fish oil in this hypertensive model.

Enhanced role of K+ channels in relaxations of hypercholesterolemic rabbit carotid artery to NO

1995 ◽  
Vol 269 (3) ◽  
pp. H805-H811 ◽  
Author(s):  
S. Najibi ◽  
R. A. Cohen
Keyword(s):  
Carotid Artery ◽  
Sodium Nitroprusside ◽  
Channel Blocker ◽  
Isometric Tension ◽  
K Channel ◽  
K Channels ◽  
Rabbit Carotid Artery ◽  
Cyclic Monophosphate ◽  
Endothelium Dependent Relaxation

Endothelium-dependent relaxations to acetylcholine remain normal in the carotid artery of hypercholesterolemic rabbits, but unlike endothelium-dependent relaxations of normal rabbits, they are inhibited by charybdotoxin, a specific blocker of Ca(2+)-dependent K+ channels. Because nitric oxide (NO) is the mediator of endothelium-dependent relaxation and can activate Ca(2+)-dependent K+ channels directly or via guanosine 3',5'-cyclic monophosphate, the present study investigated the role of Ca(2+)-dependent K+ channels in relaxations caused by NO, sodium nitroprusside, and 8-bromoguanosine 3',5'-cyclic monophosphate (8-Brc-GMP) in hypercholesterolemic rabbit carotid artery. Isometric tension was measured in rabbit carotid artery denuded of endothelium from normal and hypercholesterolemic rabbits which were fed 0.5% cholesterol for 12 wk. Under control conditions, relaxations to all agents were similar in normal and hypercholesterolemic rabbit arteries. Charybdotoxin had no significant effect on relaxations of normal arteries to NO, sodium nitroprusside, or 8-BrcGMP, but the Ca(2+)-dependent K+ channel blocker significantly inhibited the relaxations caused by each of these agents in the arteries from hypercholesterolemic rabbits. By contrast, relaxations to the calcium channel blocker nifedipine were potentiated to a similar extent by charybdotoxin in both groups. In addition, arteries from hypercholesterolemic rabbits relaxed less than normal to sodium nitroprusside when contracted with depolarizing potassium solution. These results indicate that although nitrovasodilator relaxations are normal in the hypercholesterolemic rabbit carotid artery, they are mediated differently, and to a greater extent, by Ca(2+)-dependent K+ channels. These data also suggest that K+ channel-independent mechanism(s) are impaired in hypercholesterolemia.

Detergents, dimeric G beta gamma, and eicosanoid pathways to muscarinic atrial K+ channels

1990 ◽  
Vol 258 (5) ◽  
pp. H1507-H1514 ◽  
Author(s):  
A. Yatani ◽  
K. Okabe ◽  
L. Birnbaumer ◽  
A. M. Brown
Keyword(s):  
Cold Spring Harbor ◽  
K Channel ◽  
Direct Effects ◽  
K Channels ◽  
Nonspecific Effects ◽  
Gamma Subunits ◽  
Cold Spring ◽  
Inwardly Rectifying ◽  
Channel Currents ◽  
Zwitterionic Detergent

Control experiments for the direct effects of G protein beta gamma-subunits (G beta gamma) on muscarinic atrial K+ channel [K+ (ACh)] currents have produced different results (Nature Lond. 327: 21-22, 1987; Nature Lond. 325: 296-297, 1987; Cold Spring Harbor Symp. Quant. Biol. 53: 365-373, 1989). A recent view is that stimulation is indirect via phospholipase by (PLA2) and arachidonic acid (AA) metabolites (Nature Lond. 337: 504-505, 1989). On reexamination we found that 1) the zwitterionic detergent 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulfonate (CHAPS) used to suspend beta gamma stimulates atrial K+ (ACh) currents by itself, and the effects are concentration and Mg2+ dependent; 2) CHAPS stimulates atrial ATP-sensitive K+ channel and inwardly rectifying K+ channel currents; 3) blockers of eicosanoid pathways have nonspecific effects on atrial K+, Ca2+, and Na+ channels. We have confirmed that detergent-free, hydrophilic G beta gamma-subunits inhibit K+ (ACh) currents. Stimulatory effects of dimeric G beta gamma could not be separated from stimulatory effects of detergent, and blockers of PLA2 or lipoxygenase pathways do not clearly establish the significance of these pathways to atrial K+ (ACh) currents.

Hyperkalemia alters EDHF-mediated hyperpolarization and relaxation in coronary arteries

1996 ◽  
Vol 271 (2) ◽  
pp. H760-H767 ◽  
Author(s):  
G. W. He ◽  
C. Q. Yang ◽  
W. F. Graier ◽  
J. A. Yang
Keyword(s):  
Nitric Oxide ◽  
Cardiac Surgery ◽  
Smooth Muscle ◽  
Membrane Potential ◽  
Organ Preservation ◽  
Maximal Response ◽  
K Channels ◽  
Porcine Coronary Artery ◽  
Preservation Solutions ◽  
Endothelium Dependent Relaxation

Hyperkalemic solutions are widely used to preserve organs for transplantation and for cardiac surgery. The present study was designed to test the hypothesis that hyperkalemia may alter endothelial function through a non-nitric oxide (NO) pathway, since preliminary studies have shown that the NO pathway may not be affected. Porcine coronary artery rings were studied in organ chambers. After incubation with 20 or 50 mM K+ for 1 h, the indomethacin- and NG-nitro-L-arginine+ (L-NNA)-resistant relaxation induced by A23187 or bradykinin, which could be further inhibited by tetraethylammonium but not glibenclamide, was significantly reduced. Incubation with hyperkalemia also significantly increased the concentration eliciting 50% of the maximal response to A23187 and bradykinin. A23187-induced hyperpolarization of the membrane potential was significantly reduced by hyperkalemic incubation. However, 1-h incubation with hyperkalemia does not affect the endothelial Ca2+ concentration. We conclude that exposure to hyperkalemia reduces the indomethacin- and L-NNA-resistant endothelium-dependent relaxation and endothelium-dependent hyperpolarization. This reduction in the relaxation and hyperpolarization is related to the endothelium-derived hyperpolarizing factor by affecting its effect on the smooth muscle cell, probably through partially depolarizing the membrane, and the Ca2(+)- activated K+ channels rather than by affecting its biosynthesis and/or release in the endothelial cell. Our study may suggest a new mechanism for coronary dysfunction after exposure to hyperkalemic cardioplegia and organ preservation solutions.

scholarly journals Selective Proton-Mediated Transport by Electrogenic K+-Binding Macrocycles

Chemistry ◽  
2020 ◽  
Vol 2 (1) ◽  
pp. 11-21
Author(s):  
Yu-Hao Li ◽  
Shao-Ping Zheng ◽  
Dawei Wang ◽  
Mihail Barboiu
Keyword(s):  
Ion Channels ◽  
Therapeutic Agents ◽  
K Channel ◽  
Transport Activity ◽  
Selective Activation ◽  
K Channels ◽  
High K ◽  
Carbonyl Cyanide ◽  
Self Assembled ◽  
K Transport

Synthetic K+-binding macrocycles have potential as therapeutic agents for diseases associated with KcsA K+ channel dysfunction. We recently discovered that artificial self-assembled n-alkyl-benzoureido-15-crown-5-ether form selective ion-channels for K+ cations, which are highly preferred to Na+ cations. Here, we describe an impressive selective activation of the K+ transport via electrogenic macrocycles, stimulated by the addition of the carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP) proton carrier. The transport performances show that both the position of branching or the size of appended alkyl arms favor high transport activity and selectivity SK+/Na+ up to 48.8, one of the best values reported up to now. Our study demonstrates that high K+/Na+ selectivity obtained with natural KcsA K+ channels is achievable using simpler artificial macrocycles displaying constitutional functions.

scholarly journals Nitric oxide mediates abnormal responsiveness of thyroid arteries in methimazole-treated patients

2005 ◽  
Vol 152 (4) ◽  
pp. 551-556 ◽  
Author(s):  
Joaquín Ortega ◽  
José M Vila ◽  
María Dolores Mauricio ◽  
Gloria Segarra ◽  
Pascual Medina ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Relaxation Response ◽  
Superior Thyroid Artery ◽  
Maximal Contraction ◽  
Relaxation Resistance ◽  
High K ◽  
Synthase Inhibitor ◽  
Design And Methods ◽  
Endothelium Dependent Relaxation

Objective: We studied the intervention of nitric oxide (NO), prostacyclin and endothelium-derived hyperpolarizing factor (EDHF) in mediating responses to acetylcholine in thyroid arteries from euthyroid and methimazole-treated (MT) patients. Design and methods: Branches of the superior thyroid artery were obtained from 19 euthyroid patients and 17 MT patients (euthyroid at the time of surgery) undergoing total thyroidectomy or hemithyroidectomy. Artery rings were suspended in organ baths for isometric recording of tension. Results and conclusions: Acetylcholine caused endothelium-dependent relaxation of greater magnitude in arteries from MT patients (pD2 (−log EC50) values were 7.68±0.19 in euthyroid and 8.17±0.26 in MT patients, P <0.05). The relaxation was unaffected by indomethacin and was partially reduced by the NO-synthase inhibitor NG-monomethyl-l-arginine (l-NMMA). This reduction was higher in arteries from MT patients (50±6%) as compared with euthyroid patients (36±6%) (P <0.05). Inhibition of K+ channels using apamin combined with charybdotoxin or high K+ solution abolished the relaxation resistance to l-NMMA and indomethacin. The maximal contraction response to noradrenaline (as a percentage of the response to 100 mM KCl) was lower in MT than in euthyroid patients (57±10 and 96±8 respectively, P < 0.05). The hyporesponsiveness to noradrenaline in arteries from MT patients was corrected by l-NMMA. The results indicate that: (i) thyroid arteries from MT patients show an increased relaxation response to acethylcholine and a decreased contraction response to noradrenaline due to overproduction of NO; (ii) EDHF plays a prominent role in acetylcholine-induced relaxation through activation of Ca2+-activated K+ channels; (iii) the abnormal endothelium-dependent responses in arteries from MT patients are not corrected by medical treatment.

Heterogeneous populations of K+ channels mediate EDRF release to flow but not agonists in rabbit aorta

1994 ◽  
Vol 266 (2) ◽  
pp. H590-H596 ◽  
Author(s):  
I. R. Hutcheson ◽  
T. M. Griffith
Keyword(s):  
Shear Stress ◽  
Rabbit Aorta ◽  
Katp Channels ◽  
K Channel ◽  
K Channels ◽  
Kca Channels ◽  
Endothelium Derived Relaxing Factor ◽  
Endothelium Dependent Relaxation ◽  
High Conductance

We have investigated the role of Ca(2+)- and ATP-sensitive K+ channels (KCa and KATP, respectively) in flow- and agonist-stimulated release of endothelium-derived relaxing factor (EDRF). Segments of rabbit abdominal aorta, perfused at constant flow with buffer containing indomethacin, were used as a source of EDRF in cascade bioassay, and responses to endothelium-dependent agonists were studied isometrically in rings of the same tissue in the absence of flow. Apamin, charybdotoxin (ChTX), and tetraethylammonium (TEA) were used to block a variety of low, medium, and high conductance KCa channels, and glibenclamide was used to block KATP channels. The effects of flow pulsatility were studied at pulse frequencies ranging from 0.15 to 9.75 Hz, and time-averaged shear stress was manipulated by adding dextran (80,000 mol wt) to the perfusate to increase its viscosity. Frequency-related EDRF release was maximal at approximately 5 Hz and attenuated by apamin, TEA, and ChTX, but not by glibenclamide. EDRF release stimulated by increased viscosity was attenuated by TEA, ChTX, and glibenclamide, but not by apamin. In marked contrast, EDRF release stimulated by acetylcholine and ATP was unaffected by blockade of either KCa or KATP channels. We conclude that a spectrum of KCa channel subtypes mediates endothelial transduction of the oscillatory component of pulsatile flow and that KATP channels may be additionally involved in the transduction of time-averaged shear stress. In contrast, agonist-stimulated endothelium-dependent relaxation is independent of K+ channel activation in rabbit aorta.

Inhibitory effects of the antiepileptic drug ethosuximide on G protein-activated inwardly rectifying K+ channels

2009 ◽  
Vol 56 (2) ◽  
pp. 499-506 ◽  
Author(s):  
Toru Kobayashi ◽  
Hirokazu Hirai ◽  
Masae Iino ◽  
Ichiro Fuse ◽  
Kazuhiro Mitsumura ◽  
...  
Keyword(s):  
Antiepileptic Drug ◽  
G Protein ◽  
Inhibitory Effects ◽  
K Channels ◽  
Inwardly Rectifying

scholarly journals Role of 20-HETE in mediating the effect of dietary K intake on the apical K channels in the mTAL

2001 ◽  
Vol 280 (2) ◽  
pp. F223-F230 ◽  
Author(s):  
Ruimin Gu ◽  
Yuan Wei ◽  
Houli Jiang ◽  
Michael Balazy ◽  
Wenhui Wang
Keyword(s):  
Gas Chromatography Mass Spectrometry ◽  
K Channel ◽  
Thick Ascending Limb ◽  
Patch Clamp Technique ◽  
Open Probability ◽  
Deficient Diet ◽  
K Channels ◽  
Medullary Thick Ascending Limb ◽  
High K

We have used the patch-clamp technique to study the effect of dietary K intake on the apical K channels in the medullary thick ascending limb (mTAL) of rat kidneys. The channel activity, defined by the number of channels in a patch and the open probability ( NP o), of the 30- and 70-pS K channels, was 0.18 and 0.11, respectively, in the mTAL from rats on a K-deficient diet. In contrast, NP o of the 30- and 70-pS K channels increased to 0.60 and 0.80, respectively, in the tubules from animals on a high-K diet. The concentration of 20-hydroxyeicosatetraenoic acid (20-HETE) measured with gas chromatography-mass spectrometry was 0.8 pg/μg protein in the mTAL from rats on a high-K diet and increased significantly to 4.6 pg/μg protein in the tubules from rats on a K-deficient diet. Addition of N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS) or 17-octadecynoic acid (17-ODYA), agents that inhibit the formation of 20-HETE, had no significant effect on the activity of the 30-pS K channels. However, DDMS/17-ODYA significantly increased the activity of the apical 70-pS K channel from 0.11 to 0.91 in the mTAL from rats on a K-deficient diet. In contrast, inhibition of the cytochrome P-450 metabolism of arachidonic acid increased NP o from 0.64 to 0.81 in the tubules from animals on a high-K diet. Furthermore, the sensitivity of the 70-pS K channel to 20-HETE was the same between rats on a high-K diet and on a K-deficient diet. Finally, the pretreatment of the tubules with DDMS increased NP o of the 70-pS K channels in the mTAL from rats on a K-deficient diet to 0.76. We conclude that an increase in 20-HETE production is involved in reducing the activity of the apical 70-pS K channels in the mTAL from rats on a K-deficient diet.

Basolateral K+ channels in airway epithelia. I. Regulation by Ca2+ and block by charybdotoxin

1990 ◽  
Vol 258 (6) ◽  
pp. L334-L342 ◽  
Author(s):  
J. D. McCann ◽  
J. Matsuda ◽  
M. Garcia ◽  
G. Kaczorowski ◽  
M. J. Welsh
Keyword(s):  
Recent Observation ◽  
Basolateral Membrane ◽  
Airway Epithelial Cells ◽  
K Channel ◽  
Ionophore A23187 ◽  
Airway Epithelial ◽  
Airway Epithelia ◽  
K Channels ◽  
Cl Channels ◽  
Inwardly Rectifying

In airway epithelia, adenosine 3',5'-cyclic monophosphate (cAMP) stimulates Cl- secretion by activating apical membrane Cl- channels and basolateral membrane K+ channels. Cl- channels are regulated by cAMP-dependent phosphorylation, whereas K+ channels are regulated by the cytosolic Ca2+ concentration, [Ca2+]c. Our recent observation that cAMP increases [Ca2+]c suggested that cAMP might indirectly regulate K+ channels by increasing [Ca2+]c. To study regulation of K+ channels we measured 86Rb efflux, single K+ channels in membrane patches, and [Ca2+]c with the fluorescent indicator fura-2. Isoproterenol and Ca2+ ionophore, A23187, transiently increased [Ca2+]c and transiently stimulated 86Rb efflux. Stimulation of 86Rb efflux resulted from release of intracellular Ca2+ stores. 86Rb efflux was blocked by Ba2+ or charybdotoxin, but not by tetraethylammonium. Charybdotoxin prevented all of the 86Rb efflux that was stimulated by A23187 or by forskolin. Charybdotoxin also blocked the low-conductance inwardly rectifying K+ channel (KCLIC) in membrane patches. These results indicate that the KCLIC channel is responsible for the Ca2(+)-dependent increase in K+ permeability in airway epithelial cells. They also indicate that cAMP-induced release of intracellular Ca2+ is sufficient to activate K+ channels.

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