UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The involvement of adenosine triphosphate (ATP) and carbon monoxide (CO) in the non-nitrergic nonpeptidergic component of high-frequency electrical field stimulation (EFS)-induced nonadrenergic noncholinergic (NANC) relaxation of longitudinal muscle strips from the rat gastric fundus was investigated. Under NANC conditions (1 microM atropine + 5 microM guanethidine), N(G)-nitro-L-arginine methyl ester (L-NAME, 1 mM) slightly reduced the amplitude, but did not affect the area under the curve (AUC) of EFS (13 Hz, 2 min)-induced relaxation of 9,11-dideoxy-9alpha,11alpha-methanoepoxy prostaglandin F(2alpha) (U46619, 0.1 microM)-precontracted strips. With L-NAME (1 mM) plus alpha-chymotrypsin (1 U ml(-1)), the amplitude and the AUC of relaxation were reduced to approximately two-third and one-third of controls, respectively. Pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (100 microM), apamin (0.3 microM), desensitization to ATP, suramin (100 microM), zinc protoporphyrin IX (300 microM) or ferrous haemoglobin (100 microM) did not inhibit the component of relaxation resistant to L-NAME plus alpha-chymotrypsin. L-NAME (1 mM) plus anti-vasoactive intestinal peptide (VIP) serum (1 : 100) reduced the amplitude and the AUC of relaxation to a similar extent as L-NAME (1 mM) plus alpha-chymotrypsin (1 U ml(-1)). Adding apamin (0.1 microM) to L-NAME (1 mM) plus anti-VIP serum (1 : 100) further reduced the amplitude and the AUC of relaxation. These findings suggest that the non-nitrergic nonpeptidergic component of NANC relaxation of the rat gastric fundus induced by high-frequency stimulation is mediated by a neurotransmitter that acts through apamin-sensitive mechanisms, that is neither ATP nor CO.
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PMID:Evidence for an apamin-sensitive, but not purinergic, component in the nonadrenergic noncholinergic relaxation of the rat gastric fundus. 1550 56

Non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmission has been an area of intense interest in gut motor physiology, whereas excitatory NANC neurotransmission has received less attention. In order to further explore excitatory NANC neurotransmission, we performed conventional intracellular recordings from guinea-pig taenia caeci smooth muscle. Tissue was perfused with oxygenated Krebs solution at 35 degrees C and nerve responses evoked by either oral or aboral nerve stimulation (NS) (4 square wave pulses, 0.3 ms duration, 20 Hz). Electrical activity was characterized by slow waves upon which one to three action potentials were superimposed. Oral NS evoked an inhibitory junction potential (IJP) at either the valley or peak of the slow wave. Application of nifedipine (1 microM) abolished slow waves and action potentials, but membrane potential flunctuations (1-3 mV) and IJPs remained unaffected. Concomitant application of apamin (300 nM), a small-conductance Ca(2+)-activated K(+) channel blocker, converted the IJP to an EJP that was followed by slow IJP. Further administration of N(G)-nitro-l-arginine methyl ester (l-NAME, 200 microM), a nitric oxide synthase inhibitor, abolished the slow IJP without affecting the EJP, implying that the slow IJP is due to nitrergic innervation. The EJP was abolished by tetrodotoxin (1 microM), but was not significantly affected by atropine (3 microM) and guanethidine (3 microM) or hexamethonium (500 microM). Substance P (SP, 1 microM) desensitization caused slight attenuation of the EJP, but the EJP was abolished by desensitization with alpha,beta-methylene ATP (50 microM), a P2 purinoceptor agonist that is more potent than ATP at the P2X receptor subtype, suramin (100 microM), a non-selective P2 purinoceptor antagonist, and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS, 100 microM) , a selective P2X purinoceptor antagonist. In contrast, the EJP was unaffected by MRS-2179 (2 microM), a selective P2Y(1) receptor antagonist. Aboral NS evoked an apamin- and l-NAME-sensitive IJP, but virtually no NANC EJP. These data suggest the presence of polarized excitatory purinergic neurotransmission in guinea-pig taenia caeci, which appears to be mediated by P2X purinoceptors, most likely the P2X(1) subtype.
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PMID:Excitatory purinergic neurotransmission in smooth muscle of guinea-pig [corrected] taenia caeci. 1567 92

This study examined the nitric oxide (NO) control of the vascular smooth muscle of the ventral abdominal vein and vena cava of the toad, Bufo marinus, by using anatomical and physiological approaches. Nicotinamide adenine di-nucleotide phosphate-diaphorase histochemistry and immunohistochemistry using endothelial nitric oxide synthase (NOS) and neural NOS antibodies produced no evidence for endothelial NOS in the veins, but, neural NOS-immunoreactive perivascular nerves were present. Acetylcholine (10(-5) M) caused a vasodilation in both veins that was endothelium-independent, and which was blocked by the soluble guanylyl cyclase inhibitor, ODQ (10(-5) M). The NOS inhibitors, L-NNA (10(-4) M) and L-NAME (10(-4) M), did not significantly reduce the vasodilatory effect of acetylcholine in the veins; this suggested that the vasodilation was not due to NO. However, in the presence of phenoxybenzamine (10(-7)-10(-8) M), L-NNA significantly reduced the vasodilatory effect of acetylcholine in the veins. This unusual response is due to phenoxybenzamine partially inactivating the muscarinic receptor pool in the veins. In addition, the neural NOS inhibitor, vinyl-L-NIO (10(-5) M), significantly reduced the acetylcholine-mediated vasodilation in the presence of phenoxybenzamine. The results show that in toad veins, nitrergic nerves rather than an endothelial NO system are involved in NO-mediated vasodilation.
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PMID:Nitric oxide control of large veins in the toad Bufo marinus. 1569 Jan 77

Ammonia is a neurotoxin that has been strongly implicated in the pathogenesis of hepatic encephalopathy (HE) and other neurological disorders, and astrocytes are thought to be the principal target of ammonia toxicity. While the precise mechanisms of ammonia neurotoxicity remain to be more clearly defined, altered bioenergetics and oxidative stress appear to be critical factors in its pathogenesis. It has recently been demonstrated that pathophysiological concentrations of ammonia induce the mitochondrial permeability transition (MPT) in cultured astrocytes, a process associated with mitochondrial dysfunction, and frequently caused by oxidative stress. This study investigated the potential role of oxidative stress in the induction of the MPT by ammonia. Accordingly, the effect of various antioxidants on the induction of the MPT by ammonia in cultured astrocytes was examined. Astrocytes were subjected to NH4Cl (5 mM) treatment for 2 days with or without various antioxidants. The MPT was assessed by quantitative fluorescence imaging for the mitochondrial membrane potential (DeltaPsim), employing the potentiometric dye TMRE; by changes in mitochondrial calcein fluorescence and by 2-deoxyglucose-6-phosphate (2-DG-6-P) changes in mitochondrial permeability. Astrocytes treated with ammonia significantly dissipated the DeltaPsim, which was blocked by the MPT inhibitor, cyclosporin A, caused a decrease in mitochondrial calcein fluorescence and increased 2-DG-6-P permeability into mitochondria. All of these findings are consistent with induction of the MPT. Pretreatment with SOD, catalase, desferroxamine, Vitamin E, PBN and the nitric oxide synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME), completely blocked the ammonia-induced MPT. These data provide strong evidence that oxidative stress is involved in the induction of the MPT by ammonia, and suggest that oxidative stress and the subsequent induction of the MPT contribute to the pathogenesis of HE and other hyperammonemic disorders.
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PMID:Role of oxidative stress in the ammonia-induced mitochondrial permeability transition in cultured astrocytes. 1590 47

Reactive oxygen species (ROS) such as superoxide (O2*-) and hydrogen peroxide (H2O2) are known cerebral vasodilators. A major source of vascular ROS is the flavin-containing enzyme nicotinamide adenine dinucleotide phosphate (NADPH)-oxidase. Activation of NADPH-oxidase leads to dilatation of the basilar artery in vivo via production of H2O2, but the endogenous stimuli for this unique vasodilator mechanism are unknown. Shear stress is known to activate both NADPH-oxidase and phosphatidylinositol-3 kinase (PI3-K) in cultured cells. Hence, this study used a cranial window preparation in anesthetized rats to investigate whether increased intraluminal blood flow could induce cerebral vasodilatation via the activation of NADPH-oxidase and/or PI3-K. Bilateral occlusion of the common carotid arteries to increase basilar artery blood flow caused reproducible, reversible vasodilatation. Topical treatment of the basilar artery with the NADPH-oxidase inhibitor diphenyleneiodonium (DPI) (0.5 and 5 micromol/L) inhibited flow-induced dilatation by up to 50% without affecting dilator responses to acetylcholine. Treatment with the H2O2 scavenger, catalase similarly attenuated flow-induced dilatation, suggesting a role for NADPH-oxidase-derived H2O2 in this response. The nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) partially reduced flow-induced dilatation, and combined treatment with a ROS inhibitor (DPI or catalase) and L-NAME caused a greater reduction in flow-induced dilatation than that seen with any of these inhibitors alone. Flow-induced dilatation was also markedly inhibited by the PI3-K inhibitor, wortmannin. Increased O2*- production in the endothelium of the basilar artery during acute increases in blood flow was confirmed using dihydroethidium. Thus, flow-induced cerebral vasodilatation in vivo involves production of ROS and nitric oxide, and is dependent on PI3-K activation.
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PMID:Flow-induced cerebral vasodilatation in vivo involves activation of phosphatidylinositol-3 kinase, NADPH-oxidase, and nitric oxide synthase. 1622 43

Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid that acts both as an extracellular ligand for endothelial differentiation gene receptor family and as an intracellular second messenger. Cellular levels of S1P are low and tightly regulated by sphingosine kinase (SPK). Recent studies have suggested that eNOS pathway may function as a downstream target for the biological effects of receptor-mediated S1P. Here we have studied the possible interplay between intracellular SIP generation and the eNOS activation pathway. S1P causes an endothelium-dependent vasorelaxation in rat aorta that is PTX sensitive, inhibited by L-NAME that involves eNOS phosphorylation, and mainly dependent on hsp90. When rat aorta rings were incubated with the SPK inhibitor DL-threo-dihydrosphingosine (DTD), there was a concentration-dependent reduction of Ach-induced vasorelaxation, implying a consistent contribution of sphingolipid pathway through intracellular sphingosine release and phosphorylation. Co-immunoprecipitation experiments consistently showed increased association of hsp90 with eNOS after exposure of cells to S1P as well to BK or calcium ionophore A-23187. Interestingly, as opposite to A-23187, BK and S1P effect were significantly inhibited by pretreatment with the SPK inhibitor DTD. In conclusion, our data demonstrate that an interplay exists among eNOS, hsp90, and intracellularly generated S1P where eNOS coupling to hsp90 is a major determinant for NO release as confirmed by our functional and molecular studies.
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PMID:Essential requirement for sphingosine kinase activity in eNOS-dependent NO release and vasorelaxation. 1632 29

The electron spin resonance (ESR) spin-trapping technique coupled with iron-dithiocarbamate complexes is one of the most specific methods for nitric oxide (NO) detection. In this study, we applied this method for the evaluation of the substrate and the inhibitors of NO synthase (NOS). A three-line ESR signal was detected from the mixture of inducible NOS (iNOS), l-arginine (Arg), nicotinamide adenine dinucleotide phosphate (NADPH), tetrahydrobiopterin, dithiothreitol, and Fe(2+)-N-(dithiocarboxy) sarcosine (DTCS-Fe), and the signal intensity increased time-dependently. The signal was not observed by excluding either Arg or NADPH, and it was decreased by the addition of hemoglobin, which is an NO scavenger, and N(G)-monomethyl-l-arginine (l-NMMA), N(G)-nitro-l-arginine (l-NAME), and aminoguanidine (AG), which are NOS inhibitors, depending on the concentration. In comparison with l-NAME and AG, l-NMMA strongly inhibited iNOS activity. By using this method, the K(m) value of Arg and the K(i) value of l-NMMA for iNOS were determined to be 12.6 and 6.1muM, respectively. These values are consistent with the reported values measured by the oxyhemoglobin and citrulline assays. These results suggest that the ESR spin-trapping technique coupled with the iron-dithiocarbamate complex can be applied for the evaluation of substrates and inhibitors of NOS, and it would be a powerful tool due to its simplicity and high specificity to NO.
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PMID:Application of electron spin resonance spin-trapping technique for evaluation of substrates and inhibitors of nitric oxide synthase. 1636 Jan 10

Long-acting dihydropyridine calcium channel blockades have been shown to limit the progression of atherosclerosis and decrease the incidence of cardiovascular events in humans and animals. To investigate the vasoprotective effects beyond the blood pressure-lowering effects of these agents, amlodipine (20 mg/kg/ day) and manidipine (10 mg/kg/day) were administered by gavage to N(G)-nitro-L-arginine methyl ester (L-NAME)-induced hypertensive rats for 2 weeks. L-NAME treatment (0.7 mg/ml in drinking water) significantly decreased the gene and protein expression of endothelial nitric oxide synthase (eNOS) and increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, vascular cell adhesion molecule-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) mRNA levels in the aorta, as determined by Western blotting and reverse transcription (RT)-polymerase chain reaction (PCR). Amlodipine and manidipine normalized the decreased expression of eNOS gene and protein, and attenuated the overexpression of NADPH oxidase, VCAM-1, and MCP-1 mRNA. Furthermore, amlodipine and manidipine prevented the L-NAME-induced increase in the angiotensin converting enzyme (ACE) mRNA content, thereby restoring control levels in the aorta. On the other hand, hydralazine treatment had no such effect in L-NAME treated rats. Furthermore, the increased expression of manganese superoxide dismutase (Mn-SOD) by L-NAME treatment was not affected by amlodipine, manidipine, or hydralazine. We concluded that the direct anti-inflammatory and antioxidative effects of calcium channel blockades in the aorta of rats with L-NAME-induced hypertension were not likely to have been mediated by the blood pressure-lowering action of these agents, but instead these beneficial effects appear to have been mediated by an augmentation of eNOS expression and by the inhibition of the expression of ACE.
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PMID:Calcium channel blockades exhibit anti-inflammatory and antioxidative effects by augmentation of endothelial nitric oxide synthase and the inhibition of angiotensin converting enzyme in the N(G)-nitro-L-arginine methyl ester-induced hypertensive rat aorta: vasoprotective effects beyond the blood pressure-lowering effects of amlodipine and manidipine. 1639 74

The influence of renal nerves on the effects of concurrent NO synthase inhibition (10 mg kg(-1) b.w. i.v. L-NAME) and ET(A)/ET(B) receptor inhibition (10 mg kg(-1) b.w. i.v. bosentan) on renal excretory function and blood pressure in conscious spontaneously hypertensive rats (SHR) was investigated. L-NAME increased blood pressure, urine flow rate, fractional excretion of sodium, chloride and phosphate in both normotensive Wistar rats and SHR with intact renal nerves (p<0.01). GFR or RBF did not change in any of the groups investigated. The effects of L-NAME on renal excretory function were markedly reduced by bosentan and the values returned to control level in the normotensive rats, while in SHR the values were reduced by bosentan, but they remained significantly elevated as compared to control level (p<0.05). The hypertensive response induced by L-NAME in SHR is partially due to activation of endogenous endothelins, but it does not depend on renal nerves. Chronic bilateral renal denervation abolished the effect of L-NAME on sodium and chloride excretion in normotensive rats, whereas it did not alter this effect in SHR. The participation of endogenous endothelins in changes of renal excretory function following NO synthase inhibition is diminished in SHR as compared to Wistar rats.
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PMID:Renal nerves participation in the effects of nitric oxide and ET(A)/ET(B) receptor inhibition in spontaneously hypertensive rats. 1649 95

Acetylcholine (ACh) induces nasal congestion at low doses but decongestion at high doses. The current study investigated the vascular mechanisms underlying this biphasic nasal airway response in dogs. Collecting and outflow veins from anterior and posterior nasal venous systems and the septal mucosa (containing sinusoidal venous plexuses) were isolated. The in vitro isometric tension of the vascular segments was monitored to reflect vascular reactivity. Immunohistochemical localisation of reduced nicotinamide adenine dinucleotide phosphate (NADPH)-diaphorase and endothelial nitric oxide synthase (eNOS) was performed. ACh did not affect the venous plexuses but contracted the anterior collecting vein and the outflow veins of both systems in a concentration-dependent manner; the responses were unaffected by nitro-L-arginine-methyl-ester (L-NAME). ACh relaxed posterior collecting veins at low concentrations but contracted them at higher concentrations; L-NAME enhanced the contractions but inhibited the relaxations, with the inhibition reversed by L-arginine. NADPH-diaphorase and eNOS were located predominantly in the posterior collecting veins. The fact that acetylcholine at low concentrations relaxes posterior collecting veins but contracts other collecting and outflow veins implies that the agonist in vivo may induce nasal congestion by increasing posterior blood volume. At higher concentrations, acetylcholine contracts posterior collecting veins as well, implying diminished blood volume in both venous systems, and consequently nasal decongestion. The induced contraction in posterior collecting veins is nitric oxide-independent, while the induced relaxation is nitric oxide-dependent.
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PMID:Acetylcholine induces contractile and relaxant effects in canine nasal venous systems. 1673 88

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