Endothelial ATP-sensitive potassium channels mediate coronary microvascular dilation to hyperosmolarity

1997 ◽  
Vol 273 (1) ◽  
pp. H104-H112 ◽  
Author(s):  
H. Ishizaka ◽  
L. Kuo
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Potassium Channels ◽  
Vascular Smooth Muscle ◽  
Arterial Occlusion ◽  
Katp Channels ◽  
Inward Rectifier Potassium Channels ◽  
Kca Channels ◽  
Cytochrome P 450 ◽  
Coronary Arterioles

Coronary arterial occlusion has been shown to increase osmolarity in the myocardial interstitium. Intracoronary injection of hyperosmolar solutions reduces coronary vascular resistance. However, the response of coronary microvessels to an abluminal increase in osmolarity is unclear, and the underlying mechanism for its vasomotor regulation has not been elucidated. In this regard, porcine coronary arterioles (81 +/- 2 microns) were isolated, cannulated, and pressurized for in vitro study. Hyperosmolarity (300-345 mosM) was produced by adding D-glucose or D-sucrose to the extravascular solution. After the arterioles developed a stable vascular tone, a graded vasodilation was observed when glucose or sucrose was incrementally administered. This hyperosmotic vasodilation was abolished after endothelial removal. Intraluminal administration of KCl (80 mM) or the ATP-sensitive potassium (KATP)-channel inhibitor glibenclamide (1 microM) to the intact vessels significantly attenuated the hyperosmotic vasodilation. Inhibition of inward rectifier potassium channels by a low concentration of BaCl2 (10 microM) did not affect vasodilation. However, a high concentration of BaCl2 (100 microM), which has been reported to inhibit KATP channels, attenuated the hyperosmotic vasodilation. Iberiotoxin (100 nM), a calcium-activated potassium (KCa)-channel inhibitor had no effect on hyperosmolarity-induced vasodilation. Inhibition of the synthesis of endothelial nitric oxide, prostaglandins, and arachidonic acid metabolites from cytochrome P-450 had no effect on hyperosmotic vasodilation. Furthermore, inhibition of vascular smooth muscle KATP channels and the large- and small-conductance KCa channels by extraluminal administration of glibenclamide, iberiotoxin, and apamin, respectively, did not alter vasodilation in response to hyperosmolarity. These results indicate that dilation of coronary arterioles in response to hyperosmotic stimulation requires an intact endothelium. However, the response is independent of the release of nitric oxide, prostaglandins, or cytochrome P-450-related endothelium-derived hyperpolarizing factor and is not a result of activation of KATP and KCa channels in vascular smooth muscle. It is suggested that the opening of KATP channels in vascular endothelium and subsequent hyperpolarization of that cell type mediate coronary microvascular dilation in response to hyperosmolarity.

Hydrogen peroxide induces endothelium-dependent and -independent coronary arteriolar dilation: role of cyclooxygenase and potassium channels

2003 ◽  
Vol 285 (6) ◽  
pp. H2255-H2263 ◽  
Author(s):  
Naris Thengchaisri ◽  
Lih Kuo
Keyword(s):  
Hydrogen Peroxide ◽  
Smooth Muscle ◽  
Potassium Channels ◽  
Prostaglandin E ◽  
Inward Rectifier Potassium Channels ◽  
Cytochrome P 450 ◽  
Cox 1 ◽  
Coronary Arterioles

Hydrogen peroxide, a relatively stable reactive oxygen species, is known to elicit vasodilation, but its underlying mechanism remains elusive. Here, we examined the role of endothelial nitric oxide (NO), prostaglandin, cytochrome P-450-derived metabolites, and smooth muscle potassium channels in coronary arteriolar dilation to abluminal H2O2. Pig subepicardial coronary arterioles (50–100 μm) were isolated and pressurized without flow for in vitro study. Arterioles developed basal tone and dilated dose dependently to H2O2 (1–100 μM). Disruption of th endothelium and inhibition of cyclooxygenase (COX) by indomethacin produced identical attenuation of vasodilation to H2O2. Conversely, the vasodilation to H2O2 was not affected by either the NO synthase inhibitor NG-nitro-l-arginine methyl ester or the cytochrome P-450 enzyme blocker miconazole. Inhibition of the COX-1, but not the COX-2 pathway, attenuated H2O2-induced dilation similarly to indomethacin. The production of prostaglandin E2 (PGE2), but not prostaglandin I2, from coronary arterioles was significantly increased by H2O2. Furthermore, inhibition of PGE2 receptors with AH-6809 attenuated vasodilation to H2O2 similar to that produced by indomethacin. In the absence of a functional endothelium, H2O2-induced dilation was attenuated, in an identical manner, by a depolarizing agent KCl and a calcium-activated potassium (KCa) channel inhibitor iberiotoxin. However, PGE2-induced dilation was not affected by iberiotoxin. The endothelium-independent dilation to H2O2 was also insensitive to the inhibition of guanylyl cyclase, lipoxygenase, ATP-sensitive potassium channels, and inward rectifier potassium channels. These results suggest that H2O2 induces endothelium-dependent vasodilation through COX-1-mediated release of PGE2 and also directly relaxes smooth muscle by hyperpolarization through KCa channel activation.

In vivo location and mechanism of EDHF-mediated vasodilation in canine coronary microcirculation

1999 ◽  
Vol 277 (3) ◽  
pp. H1252-H1259 ◽  
Author(s):  
Yasuhiro Nishikawa ◽  
David W. Stepp ◽  
William M. Chilian
Keyword(s):  
Nitric Oxide ◽  
Potassium Channels ◽  
Potassium Channel ◽  
Direct Evidence ◽  
Coronary Microcirculation ◽  
Combined Administration ◽  
Cytochrome P 450 ◽  
Coronary Arterioles

Responses of epicardial coronary arterioles to ACh were measured using stroboscopic fluorescence microangiography in dogs ( n = 38). ACh (0.1 and 0.5 μg ⋅ kg−1 ⋅ min−1ic) dilated small (<100 μm, 11 ± 2 and 19 ± 2%, respectively) and large (>100 μm, 6 ± 3 and 13 ± 3%, respectively) arterioles at baseline. Combined administration of N ω-monomethyl-l-arginine (l-NMMA; 1.0 μmol/min ic) and indomethacin (10 mg/kg iv) eliminated ACh-induced dilation in large coronary arterioles but only partially attenuated that in small arterioles. Suffusion of a buffer containing 60 mM KCl (high KCl) completely abolished cromakalim-induced dilation in arterioles and in combination with l-NMMA plus indomethacin completely blocked ACh-induced dilation in small arterioles. This indicated that the vasodilation to ACh that persists in small arterioles after administration of l-NMMA and indomethacin is mediated via a hyperpolarizing factor. The ACh-induced vasodilation remaining after l-NMMA and indomethacin was completely blocked by the large-conductance potassium-channel antagonist iberiotoxin or by epicardial suffusion of miconazole or metyrapone, inhibitors of cytochrome P-450 enzymes. These observations are consistent with the view that endothelium-derived hyperpolarizing factor (EDHF) is a product of cytochrome P-450 enzymes and produces vasodilation by the opening of large-conductance potassium channels. We conclude that ACh-induced dilation in large coronary arterioles is mediated mainly by nitric oxide (NO), whereas, in small arterioles both NO and EDHF mediate dilation to ACh. These data provide the first direct evidence for an in vivo role of EDHF in small coronary arterioles.

scholarly journals The phytoestrogen ginsensoside Re activates potassium channels of vascular smooth muscle cells through PI3K/Akt and nitric oxide pathways

2007 ◽  
Vol 54 (3,4) ◽  
pp. 381-384 ◽  
Author(s):  
Yutaka Nakaya ◽  
Kazuaki Mawatari ◽  
Akira Takahashi ◽  
Nagakatsu Harada ◽  
Akiko Hata ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Potassium Channels ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Muscle Cells

Potassium Channel-mediated Hyperpolarization of Mesenteric Vascular Smooth Muscle by Isoflurane 

1999 ◽  
Vol 90 (3) ◽  
pp. 779-788 ◽  
Author(s):  
Naohiro Kokita ◽  
Thomas A. Stekiel ◽  
Mitsuaki Yamazaki ◽  
Zeljko J. Bosnjak ◽  
John P. Kampine ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Potassium Channels ◽  
Vascular Smooth Muscle ◽  
Potassium Channel ◽  
Potassium Conductance ◽  
Inward Rectifier ◽  
Sprague Dawley ◽  
Resistance Arteries ◽  
Inward Rectifier Potassium Channels ◽  
Voltage Dependent

Background A primary source of calcium (Ca2+) necessary for excitation contraction in vascular smooth muscle (VSM) is influx via voltage-dependent Ca2+ channels. Thus, force generation in VSM is coupled closely to resting transmembrane potential, which itself is primarily a function of potassium conductance. Previously, the authors reported that volatile anesthetics hyperpolarize VSM of small mesenteric resistance arteries and capacitance veins. The current study was designed to determine whether isoflurane-mediated hyperpolarization is the result of specific effects on one or more of four types of potassium channels known to exist in VSM. Methods Transmembrane potentials (Em) were recorded from in situ mesenteric capacitance and resistance vessels in Sprague-Dawley rats weighing 250-300 g. In separate experiments, selective inhibitors of each of four types of potassium channels known to exist in VSM were administered in the superfusate of the vessel preparations to assess their effects on isoflurane-mediated hyperpolarization. Results Resting VSM Em ranged from -38 to -43 mV after local sympathetic denervation. Isoflurane produced a significant hyperpolarization (2.7-4.3 mV), whereas each potassium channel inhibitor significantly depolarized (2.8-8.5 mV) the VSM. Both 100 nM iberiotoxin (inhibitor of high conductance calcium-activated potassium channels) and 1 microM glybenclamide (inhibitor of adenosine triphosphatase-sensitive potassium channels) significantly inhibited VSM hyperpolarization induced by 1 MAC (minimum alveolar concentration) levels of inhaled isoflurane (0.1-0.9 mV Em change, which was not significant). In contrast, isoflurane hyperpolarized the VSM significantly despite the presence of 3 mM 4 aminopyridine (inhibitor of voltage-dependent potassium channels) or 10 microM barium chloride (an inhibitor of inward rectifier potassium channels) (3.7-8.2 mV change in VSM Em). Conclusions These results suggest that isoflurane-mediated hyperpolarization (and associated relaxation) of VSM can be attributed in part to an enhanced (or maintained) opening of calcium-activated and adenosine triphosphate-sensitive potassium channels but not voltage-dependent or inward rectifier potassium channels.

scholarly journals Mechanism of Acitretin-Induced Relaxations in Isolated Rat Thoracic Aorta Preparations

2021 ◽  
Author(s):  
Oğuzhan Ekin Efe ◽  
Tolga Reşat Aydos ◽  
Selda Emre Aydingoz
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Potassium Channels ◽  
Vascular Smooth Muscle ◽  
Thoracic Aorta ◽  
Guanylyl Cyclase ◽  
Guanosine Monophosphate ◽  
Sprague Dawley ◽  
Smooth Muscle Contractility ◽  
Relaxation Responses

Acitretin is a member of vitamin A-derived retinoids and its effect on vascular smooth muscle had not been studied yet. The aim of this study is to investigate the effect of acitretin, a retinoid, on vascular smooth muscle contractility. Thoracic aorta preparations obtained from 34 male Sprague-Dawley rats (355 ± 15 g) were studied in isolated organ baths containing Krebs-Henseleit solution. The relaxation responses were obtained with acitretin (10-12‒10-4 M) in endothelium-preserved and endothelium-denuded aorta preparations precontracted with submaximal concentration of phenylephrine. The roles of retinoic acid receptor (RAR), nitric oxide, adenylyl and guanylyl cyclase enzymes, and potassium channels in these relaxation responses were investigated. Acitretin produced concentration-dependent relaxations, which were independent of its solvent dimethylsulfoxide, in endothelium-denuded phenylephrine-precontracted thoracic aorta preparations. While incubation with the RAR antagonist (AGN193109, 10-5 M) had no effect on these relaxations; nitric oxide synthase inhibitor (L-NAME, 10-4 M), adenylyl cyclase inhibitor (SQ2253, 10-5 M), guanylyl cyclase inhibitor (ODQ, 10-6 M), and potassium channel blocker (tetraethylammonium-TEA, 10-2 M) significantly eliminated the relaxation responses induced by acitretin. Acitretin induces relaxation in rat isolated thoracic aorta preparations without endothelium, which may be mediated by nitric oxide, cyclic adenosine monophosphate and cyclic guanosine monophosphate-dependent kinases and potassium channels.

Nitric oxide directly activates calcium-dependent potassium channels in vascular smooth muscle

Nature ◽  
1994 ◽  
Vol 368 (6474) ◽  
pp. 850-853 ◽  
Author(s):  
Victoria M. Bolotina ◽  
Soheil Najibi ◽  
James J. Palacino ◽  
Patrick J. Pagano ◽  
Richard A. Cohen
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Potassium Channels ◽  
Vascular Smooth Muscle ◽  
Calcium Dependent

Mechanisms of Isoflurane-mediated Hyperpolarization of Vascular Smooth Muscle in Chronically Hypertensive and Normotensive Conditions

2001 ◽  
Vol 94 (3) ◽  
pp. 496-506 ◽  
Author(s):  
Thomas A. Stekiel ◽  
Stephen J. Contney ◽  
Naohiro Kokita ◽  
Zeljko J. Bosnjak ◽  
John P. Kampine ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Protein Kinase ◽  
Vascular Smooth Muscle ◽  
Cyclic Adenosine Monophosphate ◽  
Katp Channels ◽  
Adenosine Monophosphate ◽  
Cyclic Guanosine Monophosphate ◽  
Guanosine Monophosphate

Background The purpose of this study was to compare the effects of isoflurane on membrane and intracellular mechanisms that regulate vascular smooth muscle (VSM) transmembrane potential (Em; which is related to VSM tone) in the spontaneously hypertensive rat (SHR) model of essential hypertension and its normotensive Wistar-Kyoto (WKY) control. Methods Vascular smooth muscle Em values were measured in situ in locally denervated, superfused, intact, small (200-300-microm OD) mesenteric arteries and veins in anesthetized 9-12-week-old SHR and WKY. Effects of 1.0 minimum alveolar concentration (0.60 mM) superfused isoflurane on VSM Em were measured before and during superfusion with specific inhibitors of VSM calcium-activated (KCa) and adenosine triphosphate-regulated (KATP) potassium channels, and with endogenous mediators of vasodilatation (nitric oxide, cyclic guanosine monophosphate, protein kinase G, cyclic adenosine monophosphate, and protein kinase A). Results Isoflurane significantly hyperpolarized small arteries (5 +/- 3.4 mV) and veins (6 +/- 4.7 mV) (pooled SHR and WKY, mean +/- SD). Inhibition of KCa and KATP channels, cyclic adenosine monophosphate, and protein kinase A, but not nitric oxide, cyclic guanosine monophosphate, and protein kinase G, abolished such hyperpolarization equally in SHR and WKY vessels. Conclusions Isoflurane-induced in situ VSM hyperpolarization in denervated, small mesenteric vessels involves a similar activation of KCa and KATP channels and cyclic adenosine monophosphate, but not nitric oxide or cyclic guanosine monophosphate, second messenger pathways in both SHR and WKY. A greater isoflurane-induced VSM hyperpolarization (observed previously in neurally intact SHR vessels) suggests enhanced inhibition of elevated sympathetic neural input as a major mechanism underlying such hyperpolarization (and coupled relaxation) in this neurogenic model of hypertension.

Thrombin Prevents the Expression of Inducible Nitric Oxide Synthase in Vascular Smooth Muscle Cells by a Proteolytically-Activated Thrombin Receptor

1995 ◽  
Vol 74 (03) ◽  
pp. 980-986 ◽  
Author(s):  
Valérie B Schini-Kerth ◽  
Beate Fißithaler ◽  
Thomas T Andersen ◽  
John W Fenton ◽  
Paul M Vanhoutte ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Inducible Nitric Oxide Synthase ◽  
Muscle Cells ◽  
Thrombin Receptor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

SummaryProteolytically active forms of thrombin (α- and γ-thrombin) and thrombin receptor peptides inhibited the release of nitrite, a stable endproduct of nitric oxide, evoked by interleukin-1 β(IL-1 β) in cultured vascular smooth muscle cells while proteolytically inactive forms [D-Phe-Pro-Arg chloromethyl ketone-α-thrombin (PPACK-α- thrombin) and diisopropylphosphoryl-α-thrombin (DIP-α-thrombin)] had either no or only minimal inhibitory effects. Under bioassay conditions, perfusates from columns containing IL-1 β-activated vascular smooth muscle cells or cells treated with IL-1βplus PPACK-α-thrombin relaxed detector blood vessels. These relaxations were abolished by the inhibitor of nitric oxide synthesis, NG-nitro-L arginine. No relaxations were obtained with untreated cells or IL-1 β-treated cells in the presence of α-thrombin. The expression of inducible nitric oxide synthase mRNA and protein in vascular smooth muscle cells by IL-1 β was impaired by α-thrombin. These results demonstrate that thrombin regulates the expression of the inducible nitric oxide synthase at a transcriptional level via the proteolytic activation of the thrombin receptor in vascular smooth muscle cells

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