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

Intracellular recordings were made from neurones E-8, E-16 and E-13a in the visceral ganglion of Helix aspersa. GSPYFVamide inhibits the activity of these neurones and the role of a second messenger system in this inhibition was investigated. 8-Bromo-cGMP, 100 microM was found to potentiate this inhibition while ODQ, 100 microM, an inhibitor of guanylyl cyclase, almost completely blocked GSPYFVamide-induced inhibition. Four NO donors sodium nitroprusside, 100 microM, sodium nitrite, 1 mM, SNOG, 50 microM, and SNAP, 10-50 microM, all potentiated the GSPYFVamide-induced inhibition. L-NAME, 100-1000 microM, a competitive inhibitor of NOS, blocked the GSPYFVamide-induced inhibition. In some cases recovery was only partial. The possible role of NO in modulating the inhibitory response to GSPYFVamide is discussed.
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PMID:Evidence for the involvement of nitric oxide in the inhibitory effect of GSPYFVamide on Helix aspersa central neurones. 971 72

1. The involvement of nitric oxide (NO) in enteric neural pathways underlying reflex responses of the longitudinal muscle (LM) and circular muscle (CM) layers activated by mucosal stimulation was examined in the isolated guinea-pig distal colon. 2. A segment of colon spanned two partitions (10 mm apart), which divided the organ bath into three chambers: a recording chamber where LM and CM tension was measured; a stimulation chamber where mucosal stimulation was applied; and a middle chamber separating them. 3. Brushing the mucosa anal and oral to the recording site evoked simultaneous oral contraction and anal relaxation of both the LM and CM. 4. N omega-nitro-L-argininel-NA; 100 microM) or N omega-nitro-L-arginine methyl ester (L-NAME; 100 microM) applied to the middle chamber or stimulation chamber decreased the oral contractile response of the LM and CM (by about 30-40 %), but increased the anal relaxation (> 600 %) and exposed an anal contraction (> 1000 % increase) of both muscles. The addition of L-NA to the recording chamber reduced the anal relaxation of the LM and CM and the anal contraction of the LM, but slightly increased the anal contraction of the CM. 5. S-Nitroso-N-acetylpenicillamine (SNAP; 10 microM), an NO donor, reversed the effects of L-NA in the middle or stimulation chambers. 6. 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ; 10 microM), a soluble guanylate cyclase inhibitor, mimicked the effects of L-NAin the middle chamber or stimulation chamber, but these effects were not reversed by SNAP. 7. The oral contractile responses, and the anal relaxation and contractile responses of the LM and CM produced by L-NA in the stimulation or middle chambers, were blocked by hexamethonium (300 microM) in any chamber. Atropine (1 microM) in the recording chamber reduced the contractile responses of the LM and CM. 8. In conclusion, endogenous NO facilitates and depresses release of acetylcholine from interneurons in ascending and descending nervous pathways, respectively. These NO effects are mediated through soluble guanylate cyclase in cholinergic interneurons
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PMID:Nitric oxide modulates cholinergic reflex pathways to the longitudinal and circular muscle in the isolated guinea-pig distal colon. 976 30

Previous in vitro studies have demonstrated that the cavernous relaxation under hypoxia does not involve the endothelium dependent mechanism. However, the mechanism of nitric oxide pathway under hypoxia are not fully evaluated or understood yet in vivo. The changes of intracavernous pressure to various vasoactive substances were monitored in 45 mature male cats in vivo under normoxia and hypoxia (pH: 7.03, PO2: 25.52 mmHg, PCO2: 84.66 mmHg). L-arginine and SNAP (s-nitroso-n-acetyl-penicillamine) produced cavernous relaxation under normoxia, but not under hypoxia (n = 19, P < 0.01). The L-arginine-induced relaxations were inhibited by L-NAME (N omega-nitro-1-arginine-methyl-ester) or methylene blue under normoxia (n = 19, P < 0.01). The cavernous relaxation was 58% suppressed under hypoxia compared to normoxia with 10(-3) M/0.2 ml of acetylcholine (n = 22, P < 0.01). Moreover, L-NAME attenuated the acetylcholine-induced relaxation under normoxia, but not under hypoxia (n = 22, P < 0.05). Epinephrine suppressed the acetylcholine-induced relaxation in both conditions (n = 10, P < 0.01), while indomethacin significantly potentiated the acetylcholine-induced relaxation under normoxia compared to hypoxia (n = 6, P < 0.05). However, none of these substances responded in severe hypoxia (PO2 < 15 mmHg, n = 3). These results suggest that erectile and contractile responses are attenuated under hypoxia. The endothelium derived relaxation via nitric oxide does not play a role in cavernous relaxation under definitive hypoxia with acidosis like in ischemic priapism (PO2 < 30 mmHg, pH < 7.25).
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PMID:The role of nitric oxide in vivo feline erection under hypoxia. 978 2

The anti-inflammatory role of nitric oxide (NO) was studied in a model of hepatic ischemia-reperfusion (I/R) in rats. Male Fischer rats were subjected to 30 min of no-flow ischemia of the left and median lobes of the liver, and animals were examined for a 4-h period of reperfusion. The animals were divided into the following groups: control-vehicle; I/R-vehicle; I/R-Nomega-nitro-L-arginine methyl ester (L-NAME, 10 mg/kg iv, 10 min before reperfusion); sham control-L-NAME, and I/R-S-nitroso-N-acetyl-penicillamine (SNAP, 25 micromol/kg iv, 10 min before reperfusion, followed by 20 micromol. kg-1. h-1 in 1.0 ml saline infused for 4 h). Results showed that mean arterial blood pressure was significantly increased in the sham control-L-NAME or I/R-L-NAME groups compared with either the I/R-vehicle or I/R-SNAP groups. However, cardiac index (CI) and stroke volume index (SVI) were markedly decreased, and systemic vascular resistance index (SVRI) was dramatically increased. Interestingly, the CI and SVI in rats treated with SNAP were markedly improved over that of the I/R group. Plasma nitrate and nitrite levels were significantly decreased in the I/R-L-NAME group; however, superoxide generation in the ischemic lobes and plasma alanine aminotransferase activity were higher compared with I/R-SNAP rats. The L-NAME-induced enhancement of hepatic injury in rats with I/R may be due in part to neutrophil infiltration, which was significantly increased compared with animals subjected to I/R or I/R-SNAP. The mechanism of L-NAME-enhanced neutrophil infiltration may be due to the fact that the ratios of P-selectin and intercellular adhesion molecule 1 (ICAM-1) mRNA to glyceraldehyde-3-phosphate dehydrogenase mRNA extracted from the ischemic lobes of I/R-L-NAME rats were significantly increased when compared with the I/R-SNAP group. These results suggest that 1) endogenous NO reduces the SVRI and permits an increased CI and SVI; 2) exogenous NO further improves CI and SVI; and 3) endogenous, but not exogenous, NO decreases P-selectin and ICAM-1 mRNA expression, thereby reducing polymorphonuclear neutrophil-dependent reperfusion tissue injury.
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PMID:NO modulates P-selectin and ICAM-1 mRNA expression and hemodynamic alterations in hepatic I/R. 984 19

Our objective was to determine the precise role of endothelial nitric oxide synthase (eNOS) as a modulator of cardiac O2 consumption and to further examine the role of nitric oxide (NO) in the control of mitochondrial respiration. Left ventricle O2 consumption in mice with defects in the expression of eNOS [eNOS (-/-)] and inducible NOS [iNOS (-/-)] was measured with a Clark-type O2 electrode. The rate of decreases in O2 concentration was expressed as a percentage of the baseline. Baseline O2 consumption was not significantly different between groups of mice. Bradykinin (10(-4) mol/L) induced significant decreases in O2 consumption in tissues taken from iNOS (-/-) (-28+/-4%), wild-type eNOS (+/+) (-22+/-4%), and heterozygous eNOS(+/-) (-22+/-5%) but not homozygous eNOS (-/-) (-3+/-4%) mice. Responses to bradykinin in iNOS (-/-) and both wild-type and heterozygous eNOS mice were attenuated after NOS blockade with N-nitro-L-arginine methyl ester (L-NAME) (-2+/-5%, -3+/-2%, and -6+/-5%, respectively, P<0.05). In contrast, S-nitroso-N-acetyl-penicillamine (SNAP, 10(-4) mol/L), which releases NO spontaneously, induced decreases in myocardial O2 consumption in all groups of mice, and such responses were not affected by L-NAME. In addition, pretreatment with bacterial endotoxin elicited a reduction in basal O2 consumption in tissues taken from normal but not iNOS (-/-)-deficient mice. Our results indicate that the pivotal role of eNOS in the control of myocardial O2 consumption and modulation of mitochondrial respiration by NO may have an important role in pathological conditions such as endotoxemia in which the production of NO is altered.
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PMID:Endogenous endothelial nitric oxide synthase-derived nitric oxide is a physiological regulator of myocardial oxygen consumption. 1020 52

Nitric oxide (NO) is emerging as a key regulator of gene expression, capable of playing either positive or negative roles. The results of this study indicate that NO exerts a dual effect on cyclooxygenase-2 (COX-2) expression in human mesangial cells (HMC). Treatment of HMC with NO synthase inhibitors attenuated interleukin-1beta (IL-1beta/tumor necrosis factor-alpha (TNF-alpha)-elicited COX-2 protein and mRNA expression, suggesting a positive role of endogenous NO on COX-2 induction. However, NO donors (sodium nitroprusside [SNP] and S-nitroso-N-acetylpenicillamine [SNAP]) amplified cytokine-elicited COX-2 expression at early time points of treatment (up to 8 h for mRNA and up to 24 h for protein expression), but were inhibitory at later times. Oligonucleotide decoy experiments confirmed the importance of nuclear factor kappaB (NF-kappaB) activation for COX-2 induction by IL-1beta/TNF-alpha. Treatment with N(G)-nitro-L-arginine methyl ester (L-NAME) did not affect initial activation of NF-kappaB by IL-1beta/TNF-alpha, but unveiled an inhibitory effect of NO generation on NF-kappaB activity after 4 h. In HMC supplemented with SNP, cytokine-induced NF-kappaB activation was potentiated at early times of induction (5 to 15 min), but inhibited at later times (1 to 4 h), suggesting a dual effect of NO donors on NF-kappaB activation. Interestingly, IkappaBalpha protein levels followed a reciprocal pattern of expression: IkappaBalpha levels were lower at early times of induction in NO donor-supplemented cells; however, after 1 h of treatment, IkappaBalpha levels became higher than in cells treated only with cytokines. In the presence of SNP, cytokine-elicited IkappaBalpha mRNA induction was initially delayed, but was amplified at later times. These changes in IkappaBalpha expression could contribute to the dual effects of NO donors on NF-kappaB activation and COX-2 expression in HMC.
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PMID:Dual effect of nitric oxide donors on cyclooxygenase-2 expression in human mesangial cells. 1023 79

Cholinergic agents increase the activity of the renal Na-HCO(3) cotransporter and have been shown to stimulate the production of nitric oxide (NO) in other cells. To study the role of NO in mediating the effect of carbachol on Na-HCO(3) cotransporter, we measured the activity of the cotransporter in rabbit proximal tubule cells treated with carbachol (10(-4 )M) or the NO inhibitor, L-NAME (10(-3) M), or carbachol+L-NAME. The activity of NaHCO(3) cotransporter was measured by recovery of intracellular pH (pH(i)) in cells loaded with pH-sensitive dye, BCECF. In control cells, carbachol significantly increased Na-HCO(3) cotransporter activity while L-NAME did not affect the activity of the cotransporter but completely blocked the enhancement induced by carbachol. Carbachol increased NO production by proximal tubule cells. We also studied the effect of the NO donor, SNAP (10(-3) M), on the cotransporter incubated for 1 h in cultured proximal tubule cells. SNAP caused a similar enhancement in the activity of the cotransporter suggesting that a different NO donor is capable of enhancing the activity of the cotransporter to the same extent as that observed with carbachol. Because the effect of NO is thought to involve cGMP, we examined the effect of 8-Br-cGMP (10(-3 )M) on the cotransporter. 8-Br-cGMP caused stimulation of the Na-HCO(3) cotransporter activity although to a lesser degree than carbachol. We have previously shown that carbachol increases cytosolic calcium but the role of intracellular calcium (Ca(i)) per se on the cotransporter has not been studied. We therefore studied the role of Ca(i) on the activity of Na-HCO(3) cotransporter in rabbit proximal tubule cells by utilizing the calcium ionophore, ionomycin, the microsomal Ca-ATPase inhibitor, thapsigargin, and the calcium chelator, BAPTA. Ionomycin, 5 microM, caused a significant stimulation of Na-HCO(3) cotransporter which was prevented by BAPTA. The microsomal Ca-ATPase inhibitor, thapsigargin, also increased the cotransporter activity. As expected both ionomycin and thapsigargin caused a significant increase in Ca(i). Calyculin A, an inhibitor of protein phosphatase 2A prevented the stimulation of the cotransporter by calcium (in pH units/min: control 1.8+/-0.13; Ca 2.22+/-0.07; p<0.05; Ca+calyculin A 1.9+/-0.09, p<0.025) suggesting that calcium acting through kinases/phosphatases, plays a role in the phosphorylation of the cotransporter. These results demonstrate that NO and Ca(i) modulate the activity of the cotransporter.
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PMID:Regulation of the renal Na-HCO(3) cotransporter X. Role of nitric oxide and intracellular calcium. 1043 2

1. Central administration of bombesin inhibits gastric acid production independently of the centrally or peripherally-acting stimuli employed. This study evaluates the role and location of the cerebral nitric oxide (NO) implicated in the inhibitory effect of central bombesin on in vivo rat gastric acid secretion, as induced by distension with 15 cm H2O, insulin (0.75 u.i. kg-1 i.p.) TRH (1.2 microg kg-1, i.c.) or pentagastrin (100 microg kg-1, i.p.). 2. The acid-inhibitory effect of i.c. bombesin (40 ng kg-1) was prevented by prior administration of L-NAME (80 microg kg-1) in the dorsal motor nucleus of the vagus (DMN). This dose of L-NAME when administered into the nucleus of the tractus solitarious (NTS) did not influence the effects of bombesin. Administration of L-arginine (400 microg kg-1) into the DMN restored the acid-inhibitory effect of i.c. bombesin in animals treated with L-NAME. 3. Microinjection of bombesin (12 ng kg-1) into the paraventricular nucleus of the hypothalamus (PvN) inhibits acid secretion stimulated by pentagastrin. This inhibitory effect was prevented by a previous injection of L-NAME (80 microg kg-1) into the DMN. 4. The release of NO in the DMN following i.c. administration of bombesin was confirmed by in vivo electrochemical detection. 5. Administration by microdialysis in the DMN of the NO-donor SNAP (25 mM in 1.5 microl min-1) into the DMN inhibits pentagastrin-stimulated gastric acid secretion. 6. The present study suggests that nNOS-containing neurons in the DMN have an inhibitory role in the control of gastric acid responses.
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PMID:Synthesis of nitric oxide in the dorsal motor nucleus of the vagus mediates the inhibition of gastric acid secretion by central bombesin. 1045 16

The possible involvement of the free radical gas nitric oxide (NO) in the modulation of spinal rhythm-generating networks has been studied using Xenopus laevis larvae. Using NADPH-diaphorase histochemistry, three putative populations of nitric oxide synthase (NOS)-containing cells were identified in the brainstem. The position and morphology of the largest and most caudal population suggested that a proportion of these neurons is reticulospinal. The possible contribution of nitrergic neurons to the control of swimming activity was examined by manipulating exogenous and endogenous NO concentrations in vivo with an NO donor (SNAP, 100-500 micromol l(-)(1)) and NOS inhibitors (l-NAME and l-NNA, 0.5-5 mmol l(-)(1)), respectively. In the presence of SNAP, swim episode duration decreased and cycle period increased, whereas the NOS inhibitors had the opposite effects. We conclude from these data that the endogenous release of NO from brainstem neurons extrinsic to the spinal cord of Xenopus laevis larvae exerts a continuous modulatory influence on swimming activity, functioning like a 'brake'. Although the exact level at which NO impinges upon the swimming rhythm generator has yet to be determined, the predominantly inhibitory effect of NO suggests that the underlying mechanisms of NO action could involve modulation of synaptic transmission and/or direct effects on neuronal membrane properties.
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PMID:The distribution of NADPH-diaphorase-labelled interneurons and the role of nitric oxide in the swimming system of Xenopus laevis larvae. 1064 12

The production of endogenous nitric oxide, which regulates myocardial oxygen consumption, is decreased in heart failure. As with angiotensin-converting enzyme (ACE) inhibitors, amlodipine, a calcium antagonist, increases kinin-mediated nitric oxide production in coronary microvessels. We investigated the possibility of synergy between ACE inhibitors and amlodipine in regulating myocardial oxygen consumption. Left ventricular myocardium was isolated from 6 healthy dog hearts and 5 human hearts with end-stage heart failure at the time of orthotopic heart transplantation. Myocardial oxygen consumption was measured before and after administration of bradykinin, S-nitroso N-acetyl penicillamine (SNAP, a nitric oxide donor), ramiprilat (an ACE inhibitor), amlodipine, and the combination of a sub-threshold dose of ramiprilat (10(-8) md/L) + amlodipine. These experiments were repeated with L-nitro-arginine methyl ester (L-NAME, an inhibitor of nitric oxide synthesis), dichloroisocoumarin (an inhibitor of kinin synthesis), and HOE 140 (a B2 kinin-receptor antagonist). Baseline myocardial oxygen consumption in canine hearts was 182 +/- 21 nmol/g/min. Bradykinin and SNAP caused dose-dependent reductions in myocardial oxygen consumption (p <0.05). Ramiprilat and amlodipine caused a 10 +/- 3.2% and 11 +/- 0.8% reduction in myocardial oxygen consumption, respectively, when used alone (p <0.05). In the presence of a subthreshold dose of ramiprilat, amlodipine caused a larger (15 +/- 1.7%) reduction in myocardial oxygen consumption compared with either drug used alone (p <0.05). In human hearts, baseline myocardial oxygen consumption was 248 +/- 57 nmol/g/min. Amlodipine caused a larger reduction in myocardial oxygen consumption when used with ramiprilat (22 +/- 3.2%) as compared with amlodipine alone (15 +/- 2.6%). The effect of both drugs was attenuated by L-NAME, dichloroisocoumarin, and HOE 140 (p <0.05). In conclusion, ACE inhibitors and amlodipine act synergistically to regulate myocardial oxygen consumption by modulating kinin-mediated nitric oxide release, and this combination of drugs may be useful in the treatment of heart failure.
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PMID:Synergy of amlodipine and angiotensin-converting enzyme inhibitors in regulating myocardial oxygen consumption in normal canine and failing human hearts. 1075 May 96


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