Nitric oxide hyperpolarizes rabbit mesenteric arteries via ATP‐sensitive potassium channels.

Murphy, Michael E.; Brayden, Joseph E.

doi:10.1113/jphysiol.1995.sp020789

Cited by 339 publications

(212 citation statements)

References 38 publications

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“…In vascular smooth muscle, treatment with isosorbide dinitrate, a stimulator of soluble guanylyl cyclase, resulted in the activation of K ATP and this effect was blocked by methylene blue, an inhibitor of guanylyl cyclase (Kubo et al 1994). Similarly, treatment of mesenteric arteries with nitric oxide or lemakalim (a K ATP activator) hyperpolarized the muscle membrane (Murphy and Brayden, 1995). This hyperpolarization was suppressed by either oxyhemoglobin (a nitric oxide scavenger) or by glibenclamide.…”

Section: Discussionmentioning

confidence: 99%

“…Several of these reports indicate a linkage between the cyclic GMP signalling pathway and activation of K ATP (Lazaro-Ibanez et al 2001;Soares and Duarte 2001;Sachs et al, 2004). Indeed, studies of other cellular systems have demonstrated that cyclic GMP can lead to the activation of K ATP (Kubo et al 1994;Murphy and Brayden, 1995;Armstead 1997Armstead , 1998Schwingshackl et al 2002). These behavioral measures of the antinociceptive actions of K ATP suggest that this channel may play an important role in reversing or antagonizing the sensitizing effects of a variety of inflammatory mediators.…”

Section: Introductionmentioning

confidence: 99%

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ATP-sensitive potassium currents reduce the PGE2-mediated enhancement of excitability in adult rat sensory neurons

2007

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Behavioral studies have shown that the hyperalgesia arising from inflammatory agents, such as prostaglandin E 2 (PGE 2 ) can be antagonized by activators of the ATP-sensitive potassium current (K ATP ). This observation raises questions as to whether this suppression results from a direct action on sensory neurons and what are the cellular mechanisms giving rise to this inhibition. We found that small to medium diameter sensory neurons isolated from the L4-6 DRGs expressed the mRNAs for Kir6.1, Kir6.2, and SUR1. In perforated-patch clamp recordings from acutely dissociated sensory neurons from the young adult rat, exposure to 300 μM diazoxide, a K ATP channel agonist, significantly hyperpolarized the resting membrane potential, reduced the number of action potentials evoked by a ramp of depolarizing current, and increased the amplitude of inward K ATP currents evoked by the voltage ramp. Similar results were obtained with the protonophore FCCP, which is known to reduce the levels of intracellular ATP and lead to the activation of K ATP . Only a subpopulation of sensory neurons was sensitive to diazoxide whereas other neurons were unaffected. Treatment with 1 μM PGE 2 significantly enhanced the excitability of these small to medium diameter capsaicin-sensitive sensory neurons; this enhancement was reversed by subsequent exposure to diazoxide in a subpopulation of neurons. Similar to diazoxide, exposure to 8-Br-cyclic GMP antagonized the PGE 2 -induced increase in excitability. The effects of 8-Br-cyclic GMP could be reversed by exposure to glibenclamide, an antagonist of K ATP channels. As with diazoxide, only a subpopulation of sensory neurons were affected by 8-Br-cyclic GMP. These results demonstrate that activation of K ATP can reverse the sensitization produced by PGE 2 and may be an important means to modulate the enhanced excitability that results from inflammatory or injury conditions.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

ATP-sensitive potassium currents reduce the PGE2-mediated enhancement of excitability in adult rat sensory neurons

2007

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“…The K ATP channel opening action of nicorandil, in common with other K ATP channel openers, is usually thought to occur as a direct action on the channel (see Quayle et al, 1997 for review). It is also possible, however, that channel activation occurs through activation of GC as a result of the nitrovasodilator action of nicorandil, since nitric oxide has been reported to cause glibenclamide-sensitive hyperpolarization of rat and rabbit mesenteric arteries (Garland & McPherson, 1992;Murphy & Brayden, 1995) and isosorbide dinitrate, atrial natriuretic peptide, and 8-bromo cyclic GMP can activate K ATP channels in cultured rat aortic cells (Kubo et al, 1994). Finally, on the basis of experiments using myography and membrane potential recording in rat mesenteric artery, Fujiwara & Angus (1996) have recently suggested that nicorandil might have a third mechanism of action, causing inhibition of nifedipinesensitive Ca 2+ channels directly.…”

Section: Introductionmentioning

confidence: 99%

Potassium channel activation and relaxation by nicorandil in rat small mesenteric arteries

Davie

Kubo

Standen

1998

British J Pharmacology

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1 We used whole-cell patch clamp to investigate the currents activated by nicorandil in smooth muscle cells isolated from rat small mesenteric arteries, and studied the relaxant e ect of nicorandil using myography. 2 Nicorandil (300 mM) activated currents with near-linear current-voltage relationships and reversal potentials near to the equilibrium potential for K + . 3 The nicorandil-activated current was blocked by glibenclamide (10 mM), but una ected by iberiotoxin (100 nM) and the guanylyl cyclase inhibitor LY 83583 (1 mM). During current activation by nicorandil, openings of channels with a unitary conductance of 31 pS were detected. 4 One hundred mM nicorandil had no e ect on currents through Ca 2+ channels recorded in response to depolarizing voltage steps using 10 mM Ba 2+ as a charge carrier. A small reduction in current amplitude was seen in 300 mM nicorandil, though this was not statistically signi®cant. 5 In arterial rings contracted with 20 mM K + Krebs solution containing 200 nM BAYK 8644, nicorandil produced a concentration-dependent relaxation with mean pD 2 =4.77+0.06. Glibenclamide (10 mM) shifted the curve to the right (pD 2 =4.32+0.05), as did 60 mM K + . LY 83583 caused a dosedependent inhibition of the relaxant e ect of nicorandil, while LY 83583 and glibenclamide together produced greater inhibition than either alone. 6 Metabolic inhibition with carbonyl cyanide m-chlorophenyl hydrazone (30 nM), or by reduction of extracellular glucose to 0.5 mM, increased the potency of nicorandil. 7 We conclude that nicorandil activates K ATP channels in these vessels and also acts through guanylyl cyclase to cause vasorelaxation, and that the potency of nicorandil is increased during metabolic inhibition.

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“…NO can also increase the gastric blood fl ow by activation of ATP-sensitive potassium channels (K ATP ) (Murphy and Brayden, 1995). To evaluate the role of K ATP in the gastroprotection by NvEtOH, a pretreatment with glibenclamide (5 mg/ kg BW), a well-known blocker of these channels, was performed in the ethanol-induced gastric lesion model.…”

Section: Discussionmentioning

confidence: 99%

Gastroprotective Effect of an Ethanolic Extract from Neoglaziovia variegata (Arruda) Mez (Bromeliaceae) in Rats and Mice

Machado

Silva

Fernandes

et al. 2013

Zeitschrift Für Naturforschung C

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This study investigates the gastroprotective effect of a crude ethanolic extract of Neoglaziovia variegata (Arruda) Mez (Bromeliaceae), designated Nv-EtOH, in experimental models of gastric ulcer. In the ethanol-induced gastric ulcer model, Nv-EtOH showed gastroprotection at doses of 200 and 400 mg/kg body weight (BW) (57.0% and 79.7%, respectively). Nv-EtOH also signifi cantly reduced the formation of gastric lesions induced by ethanol/HCl (31.6% and 63.5%), ibuprofen (70.0% and 74.3%), or ischemia/reperfusion in rats (65.0% and 87.0%) at 200 and 400 mg/kg BW when compared with the vehicle group. In the antioxidant activity assessment, Nv-EtOH (400 mg/kg BW) increased the catalase activity and sulfhydryl groups (SH) levels, respectively. Moreover, gastroprotection against ethanol damage was decreased after ibuprofen pretreatment. Nv-EtOH (400 mg/kg BW) promoted a signifi cant increase in the content of gastric wall mucus. The Nv-EtOH effect was signifi cantly reduced in mice pretreated with N G -nitro-L-arginine (L-NOARG) or glibenclamide, inhibitors of nitric oxide synthase and K ATP channel activation, respectively, suggesting the involvement of these mechanisms in the Nv-EtOH-induced gastroprotective effect. Nv-EtOH decreased the total acidity, but did not modify other gastric juice parameters. Nv-EtOH was also effective in promoting the healing process in chronic gastric ulcer induced by acetic acid in rats.

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Nitric oxide hyperpolarizes rabbit mesenteric arteries via ATP‐sensitive potassium channels.

Cited by 339 publications

References 38 publications

ATP-sensitive potassium currents reduce the PGE2-mediated enhancement of excitability in adult rat sensory neurons

ATP-sensitive potassium currents reduce the PGE2-mediated enhancement of excitability in adult rat sensory neurons

Potassium channel activation and relaxation by nicorandil in rat small mesenteric arteries

Gastroprotective Effect of an Ethanolic Extract from Neoglaziovia variegata (Arruda) Mez (Bromeliaceae) in Rats and Mice

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