Nonendothelial‐derived nitric oxide activates the ATP‐sensitive K<sup>+</sup> channel of vascular smooth muscle cells

Miyoshi, Hirokazu; Nakaya, Yutaka; Moritoki, Hideki

doi:10.1016/0014-5793(94)00417-x

Cited by 103 publications

(49 citation statements)

References 17 publications

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“…33 However, no significant difference in the vascular responses observed between the diabetic patients treated with diet alone and those treated with sulfonylurea in the current study (data not shown) is consistent with the study by McVeigh et al 34 Another important factor contributing to endothelial dysfunction in diabetes mellitus is reported to be hyperglycemia in vivo. [35][36][37] In the current study, both plasma glucose and HbA1c levels were significantly higher in the diabetic patients than in the control subjects.…”

Section: Discussionsupporting

confidence: 83%

Impaired Endothelium-Dependent Vascular Responses of Retinal and Intrarenal Arteries in Patients With Type 2 Diabetes

Kawagishi

Matsuyoshi

Emoto

et al. 1999

ATVB

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Abstract-Endothelial dysfunction has been implicated in the pathogenesis of diabetic microangiopathies such as retinopathy and nephropathy as well as macrovascular diseases. The aim of the current study was to determine whether endothelial function in the retinal and renal arteries is impaired in type 2 diabetes mellitus. We examined the effects of an intravenous infusion of L-arginine and a sublingual administration of nitroglycerin on the brachial, retinal, and interlobar arterial hemodynamics in 20 type 2 diabetic patients (10 with normoalbuminuria and 10 with microalbuminuria) and 10 aged-matched control subjects. Despite no difference in the nitroglycerin-induced vascular response of the brachial or retinal artery among the 3 groups, the L-arginine-induced vascular response of each artery was significantly lower in both the normoalbuminuric and microalbuminuric patients than in the control subjects and the microalbuminuric patients showed the lowest value among the 3 groups (PϽ0.01, each artery, respectively). The L-arginineinduced vascular response of each artery was significantly correlated with HbA1c levels (brachial artery, rϭ0.617, Pϭ0.0003; retinal artery, rϭ0.599, Pϭ0.0005; interlobar artery, rϭ0.636, Pϭ0.0002). In addition, stepwise multiple regression analysis of all subjects showed that HbA1c level was an independent determinant for the L-arginine-induced vascular response of each artery. The results showed that the endothelium-dependent vascular responses of the retinal and intrarenal arteries as well as the brachial artery were impaired in diabetic patients before the clinical manifestation of diabetic nephropathy, and suggest that endothelial dysfunction in these arteries is associated with hyperglycemia in these patients. Key Words: L-arginine Ⅲ diabetes mellitus Ⅲ endothelium-dependent vasodilation Ⅲ kidney Ⅲ retina R ecently, the role of the L-arginine/nitric oxide (NO) pathway in the regulation of vascular smooth muscle tone has attracted increasing interest. NO is synthesized from the physiological precursor L-arginine by the stereospecific enzyme NO synthase. 1 NO induces relaxation of the smooth muscle by activating soluble guanylate cyclase to increase cyclic 3Ј, 5Ј-guanosine monophosphate (cGMP) levels. There is evidence from in vitro and in vivo studies that NOmediated vasodilation may be impaired in type 1 and type 2 diabetes. [2][3][4] Endothelium-derived NO has also been shown to regulate renal and ocular blood flow. [5][6][7] In isolated ophthalmic arteries, NO is an important modulator of vascular tone, 8 and systemic NO-synthase inhibition decreases choroidal blood flow in animals 9 and humans. 10 By using L-arginine analogues as probes for the renal NO pathway, several studies have demonstrated that NO acts as a potent vasodilator in the kidney. 11,12 In addition, endothelial dysfunction, as estimated by the plasma von Willebrand factor concentration, precedes and may predict the development of microalbuminuria in type 1 diabetic patients. 13 Although endothelial dysfunction i...

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Section: Discussionsupporting

confidence: 83%

Impaired Endothelium-Dependent Vascular Responses of Retinal and Intrarenal Arteries in Patients With Type 2 Diabetes

Kawagishi

Matsuyoshi

Emoto

et al. 1999

ATVB

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“…Relevant to the present study, NO has been reported to activate KATP channels in mammalian vascular smooth muscle (Miyoshi et al, 1994;Murphy and Brayden, 1995), as well as sarcolemmal (Moncada et al, 2000) and mitochondrial channels in ventricular myocytes. The latter investigators used whole-cell recording techniques to show that SNAP activated mitochondrial but not sarcolemmal KATP channels in rabbit ventricular myocytes .…”

Section: Nitric Oxidesupporting

confidence: 72%

A role for nitric oxide in hypoxia-induced activation of cardiac KATP channels in goldfish (Carassius auratus)

Cameron

Hoffmann

Zia

et al. 2003

Journal of Experimental Biology

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SUMMARY Hypoxia-induced shortening of cardiac action potential duration (APD) has been attributed in mammalian hearts to the activation of ATP-sensitive potassium (KATP) channels. Since KATP channels are also present at high densities in the hearts of vertebrate ectotherms, speculation arises as to their function during periods of reduced environmental oxygen. The purpose of the present study was to determine whether nitric oxide (NO)plays a role in cardiac sarcolemmal KATP channel activation during hypoxia in a species with a high degree of tolerance to low oxygen environments: the goldfish (Carassius auratus). Conventional intracellular and patch-clamp recording techniques were used to record responses from excised ventricles or isolated ventricular myocytes and inside-out patches, respectively, from fish acclimated at 21°C. During moderate, substrate-free hypoxia (6.1±0.2 kPa), ventricular APD was significantly shortened at 50% and 90% of full repolarization, a response that was reversible upon reoxygenation and blocked by the KATP channel antagonist BDM. Under normoxic conditions, APD was also reduced in the presence of the NO-donor SNAP (100 μmol l-1). In cell-attached membrane patches, sarcolemmal KATP channel activity was enhanced after 10 min hypoxia, an effect that was reduced or eliminated by simultaneous exposure to BDM, to the guanylate cyclase inhibitor ODQ or to the NO synthase inhibitor l-NAME. In cell-free patches, KATP channel activity was abolished by 2 mmol l-1 ATP but increased by SNAP; the cGMP analog 8-Br-cGMP (200 μmol l-1) also enhanced activity, an effect that was eliminated by BDM. Our data indicate that NO synthesized in cardiac myocytes could enhance sarcolemmal KATP channel activation during moderate hypoxia in goldfish. This response may serve a cardioprotective role by helping to conserve ATP or by reducing intracellular Ca2+ accumulation.

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“…The cGMPdependent protein kinases may be capable of phosphorylating K ATP channels and priming the channel to offer cardioprotection. 28, 29 Miyoshi et al 7 provided direct evidence that NO enhances K ATP channel activity in vascular smooth muscle cells. Recently, Sasaki et al 30 confirmed this observation by demonstrating direct activation of the mitochondrial K ATP channel with exogenously generated NO in myocytes.…”

Section: No and Intracellular Signalingmentioning

confidence: 99%

“…6 The mediator in opening of the K ATP channel after adenosine-induced protection is not known. Because NO has been proposed to open K ATP channels, 7 we hypothesized that the A 1 AR may mediate this protective effect via an NO-sensitive mechanism. We carried out the present investigation in the isolated mouse and in genetically engineered inducible nitric oxide synthase (iNOS) gene-knockout mice to provide the direct cause-andeffect relationship of iNOS in adenosine-induced delayed cardioprotection.…”

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confidence: 99%

Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A ₁ Receptors

et al. 2000

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Background-The mechanism of delayed preconditioning induced by activation of adenosine A 1 receptors (A 1 ARs) is not fully understood. We determined the role of inducible nitric oxide synthase (iNOS) in mediating adenosine-induced late cardioprotection using pharmacological inhibitors and iNOS gene-knockout mice. Methods and Results-Adult male mice were treated with saline or an A 1 AR agonist, 2-chloro-N 6 -cyclopentyladenosine (CCPA). Twenty-four hours later, the hearts were perfused in Langendorff mode and subjected to 30 minutes of global ischemia followed by 30 minutes of reperfusion. 8-Cyclopentyl-1,3-dipropylxanthine (DPCPX; 0.1 mg/kg IP) and S-methylisothiourea (SMT; 3 mg/kg IP) were used to block A 1 ARs and iNOS, respectively. Infarct size (IS) was measured by triphenyltetrazolium chloride staining, and iNOS expression was measured by Western blots. Myocardial IS was reduced from 24.0Ϯ3.2% in the saline group to 12.2Ϯ2.5% in CCPA-treated mice (PϽ0.05). The infarct-reducing effect of CCPA was abrogated by DPCPX (29.3Ϯ3.4%) and SMT (32.3Ϯ2.6%) and was absent in mice with targeted ablation of iNOS (23.9Ϯ1.6%). CCPA produced improvement in postischemic end-diastolic pressure, developed pressure, and rate-pressure product, which was also blocked by DPCPX and SMT. Increased iNOS protein expression observed in CCPA-treated hearts was diminished by DPCPX. Conclusions-Selective

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Nonendothelial‐derived nitric oxide activates the ATP‐sensitive K⁺ channel of vascular smooth muscle cells

Cited by 103 publications

References 17 publications

Impaired Endothelium-Dependent Vascular Responses of Retinal and Intrarenal Arteries in Patients With Type 2 Diabetes

Impaired Endothelium-Dependent Vascular Responses of Retinal and Intrarenal Arteries in Patients With Type 2 Diabetes

A role for nitric oxide in hypoxia-induced activation of cardiac KATP channels in goldfish (Carassius auratus)

Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A ₁ Receptors

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Nonendothelial‐derived nitric oxide activates the ATP‐sensitive K+ channel of vascular smooth muscle cells

Cited by 103 publications

References 17 publications

Impaired Endothelium-Dependent Vascular Responses of Retinal and Intrarenal Arteries in Patients With Type 2 Diabetes

Impaired Endothelium-Dependent Vascular Responses of Retinal and Intrarenal Arteries in Patients With Type 2 Diabetes

A role for nitric oxide in hypoxia-induced activation of cardiac KATP channels in goldfish (Carassius auratus)

Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A 1 Receptors

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Nonendothelial‐derived nitric oxide activates the ATP‐sensitive K⁺ channel of vascular smooth muscle cells

Inducible Nitric Oxide Synthase Mediates Delayed Myocardial Protection Induced by Activation of Adenosine A ₁ Receptors