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Inhibitor N (inhibitor + n)
Selected AbstractsRole of neuronal nitric oxide synthase in response to hypertonic saline loading in ratsACTA PHYSIOLOGICA, Issue 4 2004R. Wangensteen Abstract Aims:, This study analyses the influence of neuronal nitric oxide synthase (nNOS) blockade with 7-nitroindazole (7NI) on the haemodynamic and renal response to a hypertonic saline load (HSL). We also evaluated the effects of non-specific NOS inhibitor N, -nitro- l -arginine methyl ester (l -NAME). Methods:, The following groups were used: controls, rats treated with 7NI at 0.5 or 5 mg kg,1, and rats treated with l -NAME at 0.5 or 5 mg kg,1. A further five groups received an isotonic saline load (ISL). Results:, Mean arterial pressure (MAP) was significantly increased in control rats after HSL. MAP was further increased in both 7NI-treated groups, and the l -NAME groups showed marked dose-related pressor responses. During ISL, MAP was only significantly increased in the group treated with 5 mg kg,1 of l -NAME. The pressure,natriuresis relationship during the experimental period after the HSL was reduced in the 7NI group treated with 5 mg kg,1 and severely attenuated in both l -NAME groups. The increase in plasma sodium was significantly greater after the HSL in both 7NI groups and both l -NAME groups compared with controls. Conclusions:, The present results suggest that nNOS and other NOS isozymes play a counter-regulatory role in the pressor response to HSL. Moreover, the blockade of nNOS with the higher dose of 7NI produces a blunted pressure,natriuresis relationship in response to the HSL. Finally, it is concluded that nNOS participates in the homeostatic cardiovascular and renal response to hypertonic saline loading by attenuating the blood pressure increase and hypernatremia, and facilitating natriuresis. [source] Sensitization of meningeal nociceptors: inhibition by naproxenEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2008Dan Levy Abstract Migraine attacks associated with throbbing (manifestation of peripheral sensitization) and cutaneous allodynia (manifestation of central sensitization) are readily terminated by intravenous administration of a non-selective cyclooxygenase (COX) inhibitor. Evidence that sensitization of rat central trigeminovascular neurons was also terminated in vivo by non-selective COX inhibition has led us to propose that COX inhibitors may act centrally in the dorsal horn. In the present study, we examined whether COX inhibition can also suppress peripheral sensitization in meningeal nociceptors. Using single-unit recording in the trigeminal ganglion in vivo, we found that intravenous infusion of naproxen, a non-selective COX inhibitor, reversed measures of sensitization induced in meningeal nociceptors by prior exposure of the dura to inflammatory soup (IS): ongoing activity of A,- and C-units and their response magnitude to mechanical stimulation of the dura, which were enhanced after IS, returned to baseline after naproxen infusion. Topical application of naproxen or the selective COX-2 inhibitor N -[2-(cyclohexyloxy)-4-nitrophenyl]-methanesulfonamide (NS-398) onto the dural receptive field of A,- and C-unit nociceptors also reversed the neuronal hyper-responsiveness to mechanical stimulation of the dura. The findings suggest that local COX activity in the dura could mediate the peripheral sensitization that underlies migraine headache. [source] Involvement of Calmodulin in Glucagon-Like Peptide 1(7-36) Amide-Induced Inhibition of the ATP-Sensitive K+ Channel in Mouse Pancreatic ,-CellsEXPERIMENTAL PHYSIOLOGY, Issue 3 2001W. G. Ding The present investigation was designed to examine whether calmodulin is involved in the inhibition of the ATP-sensitive K+ (KATP) channel by glucagon-like peptide 1(7-36) amide (GLP-1) in mouse pancreatic ,-cells. Membrane potential, single channel and whole-cell currents through the KATP channels, and intracellular free Ca2+ concentration ([Ca2+]i) were measured in single mouse pancreatic ,-cells. Whole-cell patch-clamp experiments with amphotericin-perforated patches revealed that membrane conductance at around the resting potential is predominantly supplied by the KATP channels in mouse pancreatic ,-cells. The addition of 20 nM GLP-1 in the presence of 5 mM glucose significantly reduced the membrane KATP conductance, accompanied by membrane depolarization and the generation of electrical activity. A calmodulin inhibitor N -(6-aminohexyl)-5-chloro-1-naphthalenesulphonamide (W-7, 20 ,M) completely reversed the inhibitory actions of GLP-1 on the membrane KATP conductance and resultant membrane depolarization. Cell-attached patch recordings confirmed the inhibition of the KATP channel activity by 20 nM GLP-1 and its restoration by 20 ,M W-7 or 10 ,M calmidazolium at the single channel level. Bath application of 20 ,M W-7 also consistently abolished the GLP-1-evoked increase in [Ca2+]i in the presence of 5 mM glucose. These results strongly suggest that the mechanisms by which GLP-1 inhibits the KATP channel activity accompanied by the initiation of electrical activity in mouse pancreatic ,-cells include a calmodulin-dependent mechanism in addition to the well-documented activation of the cyclic AMP-protein kinase A system. [source] Combination of a urease inhibitor and a plant essential oil to control coliform bacteria, odour production and ammonia loss from cattle wasteJOURNAL OF APPLIED MICROBIOLOGY, Issue 2 2007V.H. Varel Abstract Aim:, To evaluate urea hydrolysis, volatile fatty acid (VFA) production (odour) and coliforms in cattle waste slurries after a urease inhibitor N-(n-butyl) thiophosphoric triamide (NBPT) and a plant oil component (thymol) were added. Methods and Results:, Faeces from cattle fed a diet of 70% corn silage and 30% alfalfa haylage, urine and distilled water in the ratio 50 : 35 : 15 were blended at high speed for 1 min. Triplicate aliquots of 750 ml were amended with NBPT plus or minus thymol and reblended for 1 min, and were poured into 1·6 l wide-mouth jars covered 90% with a lid. After 56 days, thymol (2000 mg kg,1 waste) in combination with NBPT (80 mg kg,1 waste) retained 5·2 g of an initial 9·2 g of urea in cattle waste slurries, compared with less than 1 g of urea retained when NBPT was the only additive (P < 0·05). Another experiment using excreta from cattle fed 76·25% high moisture corn, 19·25% corn silage and a 4·5% supplement, blended at a low speed, gave a similar response with urea hydrolysis; and the two treatments, thymol alone and thymol in combination with NBPT, reduced VFA production (P < 0·01) and eliminated all coliform bacteria by day 1. A third experiment indicated coliforms disappeared in the no addition treatment after 8 days; however, they were viable at 6·6 × 104 CFU g,1 waste beyond 35 days in the NBPT treatment. Conclusions:, Thymol supplements the effect of NBPT by increasing the inhibitory period for hydrolysis of urea in cattle waste slurries and nitrogen retention in the waste. Significance and Impact of the Study:, Thymol and NBPT offer the potential to reduce odour and pathogens in cattle manure, and increase the fertilizer value. [source] Novel glycosaminoglycan mimetic (RGTA, RGD120) contributes to enhance skeletal muscle satellite cell fusion by increasing intracellular Ca2+ and calpain activityJOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2005M. Zimowska Glycosaminoglycans (GAG) are classes of molecules that play an important role in cellular processes. The use of GAG mimetics called regenerating agent (RGTA) represents a tool to investigate the effect of GAG moiety on cellular behavior. A first member of the RGTA family (RG1192), a dextran polymers with defined amounts of sulfate, carboxymethyl, as well as hydrophobic groups (benzylamide), was shown to stimulate skeletal muscle repair after damage and myoblast differentiation. To obtain a comprehensive insight into the mechanism of action of GAG mimetics, we investigated the effect on myoblast differentiation of a novel RGTA, named RGD120, which was devoid of hydrophobic substitution and had ionic charge similar to heparin. Myoblasts isolated from adult rat skeletal muscles and grown in primary cultures were used in this study. We found that chronic treatment with RGD120 increased the growth of adult myoblasts and induced their precocious fusion into myotubes in vitro. It also partially overcame the inhibitory effect of the calpain inhibitor N -acetyl-leu-leu-norleucinal (ALLN) on these events. Western blot and zymography analyses revealed that milli calpain was slightly increased by RGD120 chronic treatment. In addition, using fluorescent probes (Indo-1 and Boc-leu-met-MAC), we demonstrated that RGD120 added to prefusing myoblast cultures accelerates myoblast fusion into myotubes, induced an increase of cytosolic free calcium concentration, and concomitantly an increase of intracellular calpain protease activity. Altogether, these results suggested that the efficiency of RGD120 in stimulating myogenesis might be in part explained through its effect on calcium mobilization as well as on the calpain amount and activity. © 2005 Wiley-Liss, Inc. [source] Quantum chemical geometry optimizations in proteins using crystallographic raw dataJOURNAL OF COMPUTATIONAL CHEMISTRY, Issue 11 2002Ulf Ryde Abstract A method is developed for the combination of quantum chemical geometry optimizations and crystallographic structure refinement. The method is implemented by integrating the quantum chemical software Turbomole with the crystallographic software Crystallography and NMR System (CNS), using three small procedures transferring information between the two programs. The program (COMQUM-X)is used to study the binding of the inhibitor N -methylmesoporphyrin to ferrochelatase, and we show that the method behaves properly and leads to an improvement of the structure of the inhibitor. It allows us to directly quantify in energy terms how much the protein distort the structure of the bound inhibitor compared to the optimum vacuum structure (4,6 kJ/mol). The approach improves the standard combined quantum chemical and molecular mechanics (QC/MM) approach by guaranteeing that the final structure is in accordance with experimental data (the reflections) and avoiding the risk of propagating errors in the crystal coordinates. The program can also be seen as an improvement of standard crystallographic refinement, providing an accurate empirical potential function for any group of interest. The results can be directly interpreted in standard crystallographic terms (e.g., R factors or electron density maps). The method can be used to interpret crystal structures (e.g., the protonation status of metal-bound water molecules) and even to locally improve them. © 2002 Wiley Periodicals, Inc. J Comput Chem 23: 1058,1070, 2002 [source] Thrombin attenuation is neuroprotective in the injured rat optic nerveJOURNAL OF NEUROCHEMISTRY, Issue 3 2001Igor Friedmann The functional loss that often follows injury of the mammalian CNS has been attributed not only to the immediate neural loss, but also to secondary neuronal degeneration caused by toxic biochemical mediators in the environment of the injured nerve. We report here that a high thrombin content, produced as a result of injury-induced activation of prothrombin, appears to be an important mediator of secondary damage. Measurement of post-traumatic neuronal survival in vivo revealed that post-traumatic local application of the thrombin inhibitor N -,-(2-naphthylsulphonylglycyl)-4-(d,l)-amidinophenylalanine piperidide acetate in the rat optic nerve subjected to mild partial crush injury left twice as many retinal ganglion cells with functioning axons as in controls. Thus, by readjusting thrombin activity, thereby possibly obtaining a moderate post-traumatic increase and thus gaining the benefit of thrombin without its toxic effects, it may be possible to create an environment that is more favourable towards post-traumatic survival. [source] Involvement of the nitric oxide/protein kinase G pathway in polychlorinated biphenyl-induced cell death in SH-SY 5Y neuroblastoma cellsJOURNAL OF NEUROSCIENCE RESEARCH, Issue 3 2006Lorella M.T. Canzoniero Abstract Polychlorinated biphenyls (PCB) are persistent environmental contaminants whose chronic exposure can affect nervous system development and function. The cellular and molecular mechanisms underlying neuronal damage are not yet clear. In the present study, we investigated whether nitric oxide (NO) could be involved in aroclor 1254 (A1254; a PCB mixture)-induced cytotoxicity in SH-SY5Y human neuroblastoma cells. Prolonged exposure (24 hr) to A1254 (10,100 ,g/ml) caused a dose-dependent reduction of cell viability that was attenuated in the presence of a calcium entry blocker, gadolinum (Gd3+) at 10 ,M, a concentration able to block voltage-sensitive calcium channels. In addition, A1254 caused an increase of cytosolic calcium that was dependent on extracellular calcium, as measured by fura-2 videomicroscopy. A1254-induced calcium rise may stimulate NO production through an activation of neuronal NOS (nNOS). Indeed, the concomitant addition of the selective nNOS inhibitor N, -propyl- L -arginine (NPLA) and A1254 prevented cell injury, suggesting that NO production plays a major role in A1254-evoked cell injury. Furthermore, the exposure (14 hr) to A1254 (30 ,g/ml) produced an up-regulation of the expression of , isoform of nNOS. This up-regulation was calcium dependent and was accompanied by an enhancement of NO production as demonstrated by an increase of nitrite formation. Moreover, A1254-induced cell injury was prevented when KT 5823, a selective cGMP/PKG inhibitor, was added concomitantly to 30 ,g/ml A1254. These results suggest that PCB-induced cell death in neuroblastoma cells is mediated by an activation of the cGMP/PKG pathway triggered by NO production. © 2006 Wiley-Liss, Inc. [source] Alternaria alternata AT Toxin Induces Programmed Cell Death in TobaccoJOURNAL OF PHYTOPATHOLOGY, Issue 10 2009Elena T. Yakimova Abstract Detached tobacco leaves were infiltrated with an AT toxin preparation from the foliar pathogen Alternaria alternata tobacco pathotype. The AT toxin preparation caused formation of necrotic lesions within 5 days post-infiltration in a concentration-dependent manner. Cell death was accompanied by increased levels of the stress metabolites hydrogen peroxide, malondialdehyde, free proline and by enhanced total protease activity. Lesion development and the production of stress metabolites were suppressed if the infiltration site was pre-infiltrated with caspase-specific peptide inhibitors (irreversible caspase-1 inhibitor acyl-Tyr-Val-Ala-Asp-chloromethylketone (Ac-YVAD-CMK) and the broad range caspase inhibitor benzyoxycarbonyl-Asp-2,6-dichlorobenzoyloxymethylketone (Z-Asp-CH2-DCB)), the serine protease inhibitor N,-p-tosyl- l -lysine chloromethylketone and the polyamine spermine. Extensive accumulation of reactive oxygen species (ROS), as determined by staining with 3-3,-diaminobenzidine and 2,,7,-dichlorofluorescein diacetate, was found in the AT toxin-challenged lesions. The data show that AT toxin-induced cell death in tobacco is a type of programmed cell death in which caspase-like proteases and ROS signalling play a prominent role. [source] Differential Central NOS-NO Signaling Underlies Clonidine Exacerbation of Ethanol-Evoked Behavioral ImpairmentALCOHOLISM, Issue 3 2010Tara S. Bender Background:, The molecular mechanisms that underlie clonidine exacerbation of behavioral impairment caused by ethanol are not fully known. We tested the hypothesis that nitric oxide synthase (NOS)-derived nitric oxide (NO) signaling in the locus coeruleus (LC) is implicated in this phenomenon. Methods:, Male Sprague,Dawley rats with intracisternal (i.c.) and jugular vein cannulae implanted 6 days earlier were tested for drug-induced behavioral impairment. The latter was assessed as the duration of loss of righting reflex (LORR) and rotorod performance every 15 minutes until the rat recovered to the baseline walk criterion (180 seconds). In a separate cohort, we measured p-neuronal NOS (nNOS), p-endothelial NOS (eNOS), and p-ERK1/2 in the LC following drug treatment, vehicle, or NOS inhibitor. Results:, Rats that received clonidine [60 Ig/kg, i.v. (intravenous)] followed by ethanol (1 or 1.5 g/kg, i.v.) exhibited synergistic impairment of rotorod performance. Intracisternal pretreatment with nonselective NOS inhibitor N, -nitro- l -arginine methyl ester (l -NAME, 0.5 mg) or selective nNOS inhibitor N -propyl- l -arginine (1 ,g) exacerbated the impairment of rotorod performance caused by clonidine,ethanol combination. Exacerbation of behavioral impairment was caused by l -NAME enhancement of the effect of ethanol, not clonidine. l -NAME did not influence blood ethanol levels; thus, the interaction was pharmacodynamic. LORR caused by clonidine (60 ,g/kg, i.v.),ethanol (1 g/kg, i.v.) combination was abolished by selective inhibition of central eNOS (l -NIO, 10 ,g i.c.) but not by nNOS inhibition under the same conditions. Western blot analyses complemented the pharmacological evidence by demonstrating that clonidine,ethanol combination inhibits phosphorylation (activation) of nNOS (p-nNOS) and increases the level of phosphorylated eNOS (p-eNOS) in the LC; the change in p-nNOS was paralleled by similar change in LC p-ERK1/2. NOS inhibitors alone did not affect the level of nitrate/nitrite, p-nNOS, p-eNOS, or p-ERK1/2 in the LC. Conclusions:, Alterations in NOS-derived NO in the LC underlie clonidine,ethanol induced behavioral impairment. A decrease in nNOS activity, due at least partly to a reduction in nNOS phosphorylation, mediates rotorod impairment, while enhanced eNOS activity contributes to LORR, elicited by clonidine,ethanol combination. [source] Nitrergic,purinergic interactions in rat distal colon motilityNEUROGASTROENTEROLOGY & MOTILITY, Issue 1 2004K. Van Crombruggen Abstract, Responses of rat distal colon circular muscle strips to exogenous nitric oxide (NO) and adenosine 5,-triphosphate (ATP) and to electrical field stimulation (EFS) were assessed in the absence/presence of various agents that interfere with nitrergic,purinergic pathways. Exogenous NO (10,6 to 10,4 mol L,1) elicited concentration-dependent, tetrodotoxin (TTX)-insensitive relaxations. The soluble guanylyl-cyclase (sGC) inhibitor 1H[1,2,4,]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) reduced duration and amplitude; the small conductance Ca2+ -sensitive K+ (SK)-channel blocker apamin (APA) only shortened the relaxations. ODQ + APA showed a marked inhibitory effect on duration and amplitude. TTX, APA, the NO-synthase inhibitor N(omega)-nitro- l -arginine methyl ester (l -NAME) and the purinergic receptor P2Y antagonist Reactive Blue 2 (RB2) shortened the relaxations by exogenous ATP (10,3 mol L,1) but did not influence the amplitude. ODQ had no effect. TTX + l -NAME did not yield a more pronounced inhibitory effect than TTX alone. The effect of ATP- , -S was similar to that of ATP. Electrical field stimulation (EFS) (40 V, 0.05 ms, 0.5,4 Hz for 30 s) yielded TTX-sensitive relaxations that were not altered by l -NAME, ODQ or RB2. APA shortened the relaxations. l -NAME + APA nearly abolished these relaxations. ODQ + APA and RB2 +l -NAME reduced the duration. These results suggest that distinct sets of small conductance SK-channels are involved in the amplitude and the duration of the relaxations and that NO increases their sensitivity to NO and ATP via guanosine 3,,5,-cyclic monophosphate (cGMP). ATP elicits relaxations via P2Y receptors with subsequent activation of SK-channels and induces neuronal release of NO. Both nitrergic and purinergic pathways must be blocked to inhibit EFS-induced relaxations. [source] Characteristics and function of cardiac mitochondrial nitric oxide synthaseTHE JOURNAL OF PHYSIOLOGY, Issue 4 2009Elena N. Dedkova We used laser scanning confocal microscopy in combination with the nitric oxide (NO)-sensitive fluorescent dye DAF-2 and the reactive oxygen species (ROS)-sensitive dyes CM-H2DCF and MitoSOX Red to characterize NO and ROS production by mitochondrial NO synthase (mtNOS) in permeabilized cat ventricular myocytes. Stimulation of mitochondrial Ca2+ uptake by exposure to different cytoplasmic Ca2+ concentrations ([Ca2+]i= 1, 2 and 5 ,m) resulted in a dose-dependent increase of NO production by mitochondria when l -arginine, a substrate for mtNOS, was present. Collapsing the mitochondrial membrane potential with the protonophore FCCP or blocking the mitochondrial Ca2+ uniporter with Ru360 as well as blocking the respiratory chain with rotenone or antimycin A in combination with oligomycin inhibited mitochondrial NO production. In the absence of l -arginine, mitochondrial NO production during stimulation of Ca2+ uptake was significantly decreased, but accompanied by increase in mitochondrial ROS production. Inhibition of mitochondrial arginase to limit l -arginine availability resulted in 50% inhibition of Ca2+ -induced ROS production. Both mitochondrial NO and ROS production were blocked by the nNOS inhibitor (4S)- N -(4-amino-5[aminoethyl]aminopentyl)- N,-nitroguanidine and the calmodulin antagonist W-7, while the eNOS inhibitor l - N5 -(1-iminoethyl)ornithine (l -NIO) or iNOS inhibitor N -(3-aminomethyl)benzylacetamidine, 2HCl (1400W) had no effect. The superoxide dismutase mimetic and peroxynitrite scavenger MnTBAP abolished Ca2+ -induced ROS generation and increased NO production threefold, suggesting that in the absence of MnTBAP either formation of superoxide radicals suppressed NO production or part of the formed NO was transformed quickly to peroxynitrite. In the absence of l -arginine, mitochondrial Ca2+ uptake induced opening of the mitochondrial permeability transition pore (PTP), which was blocked by the PTP inhibitor cyclosporin A and MnTBAP, and reversed by l -arginine supplementation. In the presence of the mtNOS cofactor (6R)-5,6,7,8,-tetrahydrobiopterin (BH4; 100 ,m) mitochondrial ROS generation and PTP opening decreased while mitochondrial NO generation slightly increased. These data demonstrate that mitochondrial Ca2+ uptake activates mtNOS and leads to NO-mediated protection against opening of the mitochondrial PTP, provided sufficient availability of l -arginine and BH4. In conclusion, our data show the importance of l -arginine and BH4 for cardioprotection via regulation of mitochondrial oxidative stress and modulation of PTP opening by mtNOS. [source] Erectile Function in Two-Kidney, One-Clip Hypertensive Rats is Maintained by a Potential Increase in Nitric Oxide ProductionTHE JOURNAL OF SEXUAL MEDICINE, Issue S3 2009A. Elizabeth Linder PhD ABSTRACT Introduction., Hypertension is closely associated with erectile dysfunction (ED) as it has been observed in many experimental models of hypertension. Additionally, epidemiological studies show that approximately a third of hypertensive patients have ED. Aim., To test the hypothesis that the two-kidney, one-clip (2K-1C) rat model of hypertension displays normal erectile function due to increased nitric oxide (NO) production in the penis. Methods., Ganglionic-induced increase in intracavernosal pressure (ICP)/mean arterial pressure (MAP) ratio was used as an index of erectile function in 2K-1C and in normotensive sham-operated (SHAM) anesthetized rats. Cavernosal strips from hypertensive and normotensive rats were used for isometric tension measurement. The contraction induced by alpha-adrenergic agonist phenylephrine and the relaxation induced by the NO donor sodium nitroprusside (SNP) and by the Rho-kinase inhibitor Y-27632 were performed in the absence and in the presence of the NO synthase inhibitor N, -nitro-L-arginine (L-NNA). Results., Changes in ICP/MAP induced by ganglionic stimulation were not different between 2K-1C and SHAM rats. The contractile response induced by phenylephrine as well as the relaxation induced by SNP or the Y-27632 were similar in cavernosal strips from both groups. However, in the presence of L-NNA, the relaxation induced by Y-27632 was significantly impaired in 2K-1C compared to SHAM. Conclusions., These data suggest that hypertension and ED could be dissociated from high levels of blood pressure in some animal models of hypertension. Erectile function in 2K-1C hypertensive rats is maintained in spite of the increased Rho-kinase activity by increased NO signaling. Linder AE, Dorrance AM, Mills TM, Webb RC, and Leite R. Erectile function in two-kidney, one-clip hypertensive rats is maintained by a potential increase in nitric oxide production. J Sex Med 2009;6(suppl 3):279,285. [source] Mechanisms influencing the vasoactive effects of lidocaine in human skin,ANAESTHESIA, Issue 2 2007D. J. Newton Summary The vasodilator properties of lidocaine are believed to be due mainly to the inhibition of action potentials via sodium channel blocking in vasoconstrictor sympathetic nerves. However, mechanisms involving the vascular endothelium may also play a role, and in this study we investigated the potential influences of nitric oxide release, the cyclo-oxygenase pathway and the ,-adrenoceptors of vascular smooth muscle. Laser Doppler imaging was used to measure microvascular blood flow responses to intradermal injection of lidocaine 2%, with or without the addition of preservatives, in eight healthy, male volunteers. Co-injection of the nitric-oxide,synthase inhibitor N,-nitro- l -arginine methyl ester caused a 60% reduction in the response after about 20 min, and this reduction was enhanced with the lidocaine solution containing the preservatives methylhydroxybenzoate and propylhydroxybenzoate. No reduction in response was seen after blocking the cyclo-oxygenase or ,-adrenoceptor pathways. Nitric oxide release contributes to the vasoactivity of lidocaine in human skin. [source] | |||||||||||||||||||||||||