Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isoflurane induces cerebral hyperemia. We sought to assess whether isoflurane induces cerebral microvessel dilation in vivo, and if so, to determine whether nitric oxide (NO) and endothelium are involved. By using a rat closed cranial window model, pial arterioles and venules of 30-70 microns in diameter were measured using intravital microscopy. The cerebral microvascular dilatory response was recorded as percent change of diameter from baseline. The pial vessels were suffused with sodium nitroprusside (SNP) or S-nitroso-acetyl-penicillamine (SNAP) to verify intact vascular smooth muscle relaxation function, and with adenosine diphosphate (ADP) and/or acetylcholine (ACh) to verify endothelial NO-generating capability. To isolate NO's role in the cerebral microvascular effects of isoflurane (Protocol I), microvessels were studied with and without nitric oxide synthase (NOS) inhibition by topically applied nitro-L-arginine methyl ester (L-NAME). In controls, L-NAME was replaced by its inactive enantiomer, nitro-D-arginine methyl ester (D-NAME). Mercury light plus fluorescein dye (LD) endothelial injury (Protocol II) was used to delineate an endothelium-mediated mechanism. Subsequently, vasodilator applications were repeated to verify the desired effects of the interventions and followed by suffusion of isoflurane 1%, 2%, and 3% (Protocol I) or isoflurane 3% (Protocol II). Suffusions of SNP, ADP, and ACh induced diameter increases of 15%-30%. NOS inhibition with L-NAME greatly attenuated ADP and ACh responses, but did not alter the SNP response, confirming that NO generation was blocked, but not NO action. These responses were unaffected in D-NAME-suffused rats. Isoflurane dilated arterioles 17% and venules 6% in the presence of D-NAME suffusion.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Role of nitric oxide and endothelium in rat pial vessel dilation response to isoflurane. 797 5

Blood pressure elevations after nitric oxide inhibition may result in part from increased sympathetic tone. In this study arterial baroreceptor reflex control of heart rate, renal sympathetic nerve activity (RSNA), and adrenal sympathetic nerve activity (ASNA) were compared in rats given normal tap water or a 3.7 nmol/L (10 mg%) solution of NG-nitro-L-arginine methyl ester (L-NAME) for 1 or 5 weeks. L-NAME raised blood pressure after 5 weeks of treatment (153 +/- 3 versus 130 +/- 3 and 124 +/- 2 mm Hg, 5 weeks versus 1 week and control). The sensitivity of arterial baroreceptor reflex control of RSNA was reduced after both 1 and 5 weeks of treatment (-5.05 +/- 0.63% and -4.46 +/- 0.2% versus -6.43 +/- 0.39% baseline activity per millimeters of mercury). Set point gain of ASNA was attenuated after 5 weeks of treatment compared with controls (-1.7 +/- 3% versus -3.3 +/- 3% baseline activity per millimeters of mercury). Maximal inhibition of ASNA was attenuated in groups treated 1 and 5 weeks (60 +/- 3% and 66 +/- 3% versus 34 +/- 4% baseline activity). The maximal increase in both RSNA and ASNA was elevated in rats treated 5 weeks (RSNA: control, 263 +/- 19%; 1 week, 224 +/- 17%; 5 weeks, 324 +/- 20%; ASNA: control, 272 +/- 29%; 1 week, 252 +/- 31%; 5 weeks, 361 +/- 28% baseline activity). The data indicate that chronic L-NAME treatment alters arterial baroreceptor reflexes in part before the onset of hypertension.
 ...
PMID:Sympathetic baroreceptor responses after chronic NG-nitro-L-arginine methyl ester treatment in conscious rats. 820 39

Nitric oxide (NO) is an important factor in tissue trauma, but its detailed role in the pathogenesis remains unknown. In autoimmune vasculitis, it is possible that NO in one of the factors underlying tissue trauma and induction of autoimmune antibodies. To study its role on an animal model using mercury chloride (HgCl2), Brown Norway rats (BN rats) were given five injections of] HgCl2, each 1 mg/kg, over 10 days. Vasculitis and production of some autoimmune antibodies developed after HgCl2 injections. Urine nitrate/nitrite, metabolic production of NO, was produced in advance of the production of other autoimmune antibodies. To elucidate the role of NO, NG-nitro-L-arginine methyl ester (L-NAME), which is a nitric oxide synthase (NOS) inhibitor, was given in addition to HgCl2, at the daily dose of 30 mg/kg. There was no difference in production of autoimmune antibodies between this group and the control group, but urine protein excretion was suppressed in the HgCl2 + L-NAME group (p < 0.001). By immunohistochemical study, inducible NOS was positive in small vessels and mesangial cells in rat kidney. We conclude that in this animal model, over-production of NO leads to the production of autoimmune antibodies and inhibition of NOS production ameliorates proteinuria. These results suggest that NO plays an important role in the induction of renal injury in the rat model of autoimmune vasculitis.
 ...
PMID:[The role of nitric oxide in mercury chloride-induced vasculitis in the brown Norway rat]. 928 9

Previous studies using the fawn-hooded hypertensive (FHH) rat have indicated that genetic factors appear to be important in determining the susceptibility to develop renal damage. This was further investigated by comparing the effects of N(omega)-nitro-L-arginine methyl ester (L-NAME) induced hypertension on functional and structural renal damage in two normotensive strains, the resistant August x Copenhagen Irish rat (ACI) and the normotensive fawn-hooded (FHL) rat, which also appears to carry a susceptibility locus for renal failure. Male rats were studied during chronic treatment with L-NAME in either a low dose (LD, 75 to 100 mg/L drinking fluid) or a high dose (HD, 175 to 250 mg/L). Survival of FHL rats was adversely affected by L-NAME treatment. All FHL-HD and 6 of 14 FHL-LD rats died before the end of the 11 weeks of follow-up, whereas all treated ACI rats except for one ACI-HD animal survived. In both strains, L-NAME caused a dose dependent increase in systolic blood pressure (SBP). However, at similar levels of SBP, the increase in albuminuria (UaV) was significantly higher in FHL compared with ACI, as was the incidence of glomerulosclerosis (GS). Both the SBP and the blood pressure burden (SBP-Av), defined as SBP averaged over the period of follow-up, directly correlated with UaV and GS in both strains. However, the increase in the degree of renal damage per millimeter of mercury increase in SBP or SBP-Av was significantly higher in the FHL than in the ACI rats. Our findings clearly show that FHL rats are more susceptible to developing renal damage after induction of hypertension by chronic L-NAME treatment. We conclude that there is an interaction between blood pressure and the genetic susceptibility to renal disease in the FHL rat.
 ...
PMID:Difference in susceptibility of developing renal damage in normotensive fawn-hooded (FHL) and August x Copenhagen Irish (ACI) rats after N(omega)-nitro-L-arginine methyl ester induced hypertension. 937 Mar 81

This study investigated the effects of C7 and C9 aliphatic (n-heptane, n-nonane), naphthenic (methylcyclohexane, 1,2,4-trimethylcyclohexane (TMCH)) and aromatic (toluene, 1,2,4-trimethylbenzene (TMB)) hydrocarbons on the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) in rat brain synaptosome fraction. Methyl mercury (MeHg) was included as a positive control. Exposure of the synaptosomes to the hydrocarbons produced a concentration-dependent linear increase in the formation of the fluorescence of 2',7'-dichlorofluorescein (DCF) as a measure of the production of ROS and RNS. Formation of RNS was demonstrated by preincubation of the synaptosome fraction with the neuronal nitric oxide synthase (nNOS) inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME), which reduced the MeHg and TMCH-stimulated fluorescence by 51% and 65%, respectively. The naphthenic hydrocarbon TMCH showed the strongest potential for ROS and RNS formation in rat brain synaptosomes, followed by TMB, toluene, n-nonane, n-heptane, and methylcyclohexane, respectively. TMCH was selected for mechanistic studies of the formation of ROS. Both MeHg and TMCH induced an increase in intracellular calcium concentration [Ca(2+)]i as measured with Fura-2. Blockade of voltage-dependent Ca(2+) channels with lanthanum prior to stimulation with MeHg and TMCH led to a reduction in the ROS/RNS formation of 72% and 70%, respectively. Furthermore, addition of cyclosporin A (CSA), a blocker of the mitochondrial permeability transition pore (MTP), lowered both the MeHg and TMCH-elevated DCF fluorescence by 72% and 59%. Preincubation of the synaptosome fraction with the protein tyrosine kinase inhibitor genistein lowered the MeHg and TMCH-stimulated fluorescence by 85% and 91%, respectively. Addition of the extracellular signal-regulated protein kinase (MEK)-1 and -2 inhibitor U0126 reduced the fluorescence stimulated by MeHg and TMCH by 62% and 63%. Furthermore, the protein kinase C inhibitor bisindolylmaleimide reduced the fluorescence stimulated by MeHg and TMCH by 52% and 56%. The compound 1-(6-[17beta-3-methoxyestra- 1,3,5(10)-trien- 17-yl]-aminohexyl)-1H-pyrrole-2,5-dione (U73122), which inhibits phospholipase C, was shown to decrease the ROS and RNS formation induced by MeHg and TMCH by 49% and 64%, respectively. The phospholipase A2 (PLA2) inhibitor 7,7-dimethyl eicosadienoic acid (DEDA) reduced fluorescence in response to MeHg and TMCH by 49% and 54%. Simultaneous addition of L-NAME, CSA, and DEDA to the synaptosome fraction totally abolished the DCF fluorescence. In conclusion, C7 and C9 aliphatic, naphthenic, and aromatic hydrocarbons stimulated formation of ROS and RNS in rat brain synaptosomes. The naphthenic hydrocarbon TMCH stimulated formation of ROS and RNS in the synaptosomes through Ca(2+)-dependent activation of PLA2 and nNOS, and through increased transition permeability of the MTP. Exposure of humans to the naphthenic hydrocarbon TMCH may stimulate formation of free radicals in the brain, which may be a key factor leading to neurotoxicity.
 ...
PMID:The effect of aliphatic, naphthenic, and aromatic hydrocarbons on production of reactive oxygen species and reactive nitrogen species in rat brain synaptosome fraction: the involvement of calcium, nitric oxide synthase, mitochondria, and phospholipase A. 1137 3

Mercury and its derivatives are known to constrict vascular smooth muscle cells. However, little is known about the role of endothelial cells in mercury-induced vasoreactivity. Using isolated, norepinephrine preconstricted rat aorta and pulmonary artery rings with intact endothelium, we demonstrate that mercury chloride (HgCl2) induces an endothelial-dependent vasorelaxation which was totally blocked by the nitric oxide inhibitor L-NAME. Besides this vasorelaxant effect, treatment with HgCl2 resulted in functional and morphological alterations of the endothelial cells. On aortic rings, endothelial cells were partly lifted from the basal membrane when incubated for 20 min in HgCl2 (10(-7) M)-containing buffer. At a concentration of 10(-6) M, the endothelial cells were completely denuded and acetylcholine vasorelaxation was abolished. Endothelial cell structure and function was preserved by incubating the vessels in HgCl2-containing rat blood instead of buffer. We conclude that HgCl2 induces an endothelial-dependent vasorelaxation and alters structure and function of vascular endothelial cells.
 ...
PMID:Nitric oxide-dependent vasorelaxation and endothelial cell damage caused by mercury chloride. 1458 Jul 85

Exposure to mercury at nanomolar level affects cardiac function but its effects on vascular reactivity have yet to be investigated. Pressor responses to phenylephrine (PHE) were investigated in perfused rat tail arteries before and after treatment with 6 nM HgCl2 during 1 h, in the presence (E+) and absence (E-) of endothelium, after L-NAME (10(-4) M), indomethacin (10(-5 )M), enalaprilate (1 microM), tempol (1 microM) and deferoxamine (300 microM) treatments. HgCl2 increased sensitivity (pD2) without modifying the maximum response (Emax) to PHE, but the pD2 increase was abolished after endothelial damage. L-NAME treatment increased pD2 and Emax. However, in the presence of HgCl2, this increase was smaller, and it did not modify Emax. After indomethacin treatment, the increase of pD2 induced by HgCl2 was maintained. Enalaprilate, tempol and deferoxamine reversed the increase of pD2 evoked by HgCl2. HgCl2 increased the angiotensin converting enzyme (ACE) activity explaining the result obtained with enalaprilate. Results suggest that at nanomolar concentrations HgCl2 increase the vascular reactivity to PHE. This response is endothelium mediated and involves the reduction of NO bioavailability and the action of reactive oxygen species. The local ACE participates in mercury actions and depends on the angiotensin II generation.
 ...
PMID:Low nanomolar concentration of mercury chloride increases vascular reactivity to phenylephrine and local angiotensin production in rats. 1809 79

Increased cardiovascular risk after mercury exposure has been described, but the underlying mechanisms are not well explored. We analyzed the effects of chronic exposure to low mercury concentrations on endothelium-dependent responses in aorta and mesenteric resistance arteries (MRA). Wistar rats were treated with mercury chloride (1st dose 4.6 microg/kg, subsequent dose 0.07 microg.kg(-1).day(-1) im, 30 days) or vehicle. Blood levels at the end of treatment were 7.97 +/- 0.59 ng/ml. Mercury treatment: 1) did not affect systolic blood pressure; 2) increased phenylephrine-induced vasoconstriction; 3) reduced acetylcholine-induced vasodilatation; and 4) reduced in aorta and abolished in MRA the increased phenylephrine responses induced by either endothelium removal or the nitric oxide synthase (NOS) inhibitor N(G)-nitro-l-arginine methyl ester (l-NAME, 100 microM). Superoxide dismutase (SOD, 150 U/ml) and the NADPH oxidase inhibitor apocynin (0.3 mM) decreased the phenylephrine-induced contraction in aorta more in mercury-treated rats than controls. In MRA, SOD did not affect phenylephrine responses; however, when coincubated with l-NAME, the l-NAME effect on phenylephrine response was restored in mercury-treated rats. Both apocynin and SOD restored the impaired acetylcholine-induced vasodilatation in vessels from treated rats. Endothelial NOS expression did not change in aorta but was increased in MRA from mercury-treated rats. Vascular O2(-) production, plasmatic malondialdehyde levels, and total antioxidant status increased with the mercury treatment. In conclusion, chronic exposure to low concentrations of mercury promotes endothelial dysfunction as a result of the decreased NO bioavailability induced by increases in oxidative stress. These findings offer further evidence that mercury, even at low concentrations, is an environmental risk factor for cardiovascular disease.
 ...
PMID:Low mercury concentrations cause oxidative stress and endothelial dysfunction in conductance and resistance arteries. 1859 95

In this work, a headspace-solid-phase micro-extraction (HS-SPME) combined with gas chromatography-mass spectrometry (GC-MS) method for multielemental speciation of organometallic compounds of mercury, lead and tin in water samples was upgraded by the introduction of tandem mass spectrometry (MS/MS) as detection technique. The analytical method is based on the ethylation with NaBEt(4) and simultaneous headspace-solid-phase micro-extraction of the derivative compounds followed by GC-MS/MS analysis. The main experimental parameters influencing the extraction efficiency such as derivatisation time, extraction time and extraction temperature were optimized. The overall optimum extraction conditions were the following: a 50 microm/30 microm divinyl-benzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) SPME fibre, 150 min derivatisation time, 15 min extraction time, sample agitation at 250 rpm and 40 degrees C extraction temperature. The analytical characteristics of the HS-SPME method combined with GC-MS and GC-MS/MS were evaluated. The combination of both techniques HS-SPME and GC-MS/MS allowed to attain lower limits of detection (4-33 ng l(-1)) than those obtained by HS-SPME-GC-MS (17-45 ng l(-1)). The proposed method presented good linear regression coefficients (r(2)>0.9970) and repeatability (4.8-21.0%) for all the compounds under study. The accuracy of the method measured as the average percentage recovery of the compounds in spiked river water and seawater samples was higher than 80% for all the compounds studied, except for monobutyltin in the river water sample. A study of the uncertainty associated with the analytical results was also carried out.
 ...
PMID:Optimisation of a headspace-solid-phase micro-extraction method for simultaneous determination of organometallic compounds of mercury, lead and tin in water by gas chromatography-tandem mass spectrometry. 1950 90

Chronic mercury exposure impairs vascular function, leading to the depression of endothelium-dependent vasodilatation. Loss of the nitric oxide (NO) pathway has been implicated, but little is known about effects on other endothelial mediators. This study investigated the mechanisms of endothelial dysfunction in rats subjected to chronic mercury chloride exposure. The endothelium-dependent relaxation of rat aorta evoked by acetylcholine (ACh) and isoproterenol was impaired in a dose-dependent manner by chronic mercury chloride exposure. Endothelium-independent responses to sodium nitroprusside (SNP) were not affected by chronic mercury chloride exposure. In healthy vessels, ACh-induced relaxation was inhibited by L-N-nitroarginine methyl ester (L-NAME; 10(-4) M) and partially by glybenclamide (10(-5) M), indicating the involvement of NO and endothelium-derived hyperpolarizing factor (EDHF). In vessels from mercury-exposed rats, responses to ACh were insensitive to L-NAME but were significantly reduced by glybenclamide, indicating selective loss of NO-mediated relaxation. In vessels from mercury-exposed rats, responses to ACh were partially restored after treatment with the antioxidant, superoxide dismutase (SOD) and catalase, this effect was not seen when aorta from exposed group was incubated with L-NAME along with SOD and catalase indicating selective loss of NO-mediated vasodilatation and with no affect the EDHF-mediated component of relaxation. The results imply that chronic mercury exposure selectively impairs the NO pathway as a consequence of oxidative stress, while EDHF is able to maintain endothelium-dependent relaxation at a reduced level.
 ...
PMID:Persistence of EDHF pathway and impairment of the nitric oxide pathway after chronic mercury chloride exposure in rats: mechanisms of endothelial dysfunction. 2114


1 2 Next >>