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)

The ability of prostaglandin E1 (PGE1) and nitric oxide (NO) donor compounds such as sodium nitroprusside (SNP), glyceryl trinitrate (GTN), and 3-morpholino-sydnonimine (SIN-1) to modulate the histamine- and bradykinin-induced increase in microvascular permeability have been investigated in rabbit skin. The effect of the NO synthesis inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) on the plasma exudation induced by histamine and bradykinin was also studied. Local edema formation was evaluated using [125I]human serum albumin. New Zealand white rabbits received an intravenous injection of [125I]human albumin followed immediately by the intradermal injection of edematogenic agents into the shaved dorsolateral skin. PGE1 (0.1 nmol/site) significantly potentiated both histamine- and bradykinin-induced edema. In contrast, SNP (0.4-400 nmol/site), SIN-1 (0.4-400 nmol/site), and GTN (0.4-40 nmol/site) did not affect the edematogenic response induced by either histamine or bradykinin. GTN (0.4-40 nmol/site) also had no effect on the increase in plasma exudation induced by histamine and bradykinin in the presence of PGE1. L-NAME (50-400 nmol/site, but not its enantiomer D-NAME, dose-dependently reduced the edema formation induced by a combination of either histamine or bradykinin with PGE1. This inhibition was significantly reversed by SNP (4-400 nmol/site) and by high doses (2.5 mumol/site) of L-arginine (but not by D-arginine). Our results thus demonstrate that PGE1, but not nitrovasodilators, can actually potentiate histamine- and bradykinin-induced edema in rabbit skin.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Dissimilarity between prostaglandin E1 and nitric oxide donors as potentiators of plasma exudation in the rabbit skin in vivo. 764 62

1. We have investigated the correlation between relaxation and changes in cyclic nucleotide content of human tracheal smooth muscle (HTSM) in vitro following inhibitory non-adrenergic non-cholinergic (i-NANC) neural bronchodilator responses evoked by electrical field stimulation (EFS), and compared these with changes seen with sodium nitroprusside (SNP), 3-morpholinosydnonimine (SIN-1) and vasoactive intestinal peptide (VIP). The effects of N omega-nitro-L-arginine methyl ester (L-NAME), Methylene Blue and alpha-chymotrypsin (alpha-CT) were studied. 2. EFS (10 Hz, 1 ms, 40 V for 30 s) evoked a time-dependent relaxation accompanied by a concurrent rise in cGMP, both of which were maximal at 30 s and unaffected by epithelium removal. Levels of cAMP were more variable than those of cGMP and were not significantly changed at any time point. 3. SIN-1 (1 mM) and SNP (100 microM) also produced time-dependent relaxations which were maximal between 2 and 8 min, accompanied by concomitant rises in cGMP; however, these changes were larger than those associated with i-NANC relaxations. cAMP levels were unchanged at all time points. 4. EFS-evoked i-NANC relaxations and cGMP increases (time, t = 30 s) were inhibited by L-NAME. The effects were partially reversed by L-arginine (1 mM), but not by D-arginine. D-NAME and alpha-CT (2 u ml-1) had no effect on either relaxation or cGMP accumulation. Tetrodotoxin (TTX, 3 microM) inhibited both relaxation and cGMP accumulation. 5. VIP (1 microM) also produced a time-dependent relaxation associated with a concurrent rise in cAMP levels with no change in cGMP levels. 6. Methylene Blue (10 microM) partially inhibited EFS (10 Hz)-evoked i-NANC relaxation and cGMP accumulation, and almost completely inhibited both relaxation and cGMP accumulation evoked by SIN-1 (1 mM). Methylene Blue had no significant effect on relaxation or cGMP accumulation evoked by SNP (100 microM). 7. Neural i-NANC relaxations in HTSM are associated with a concurrent selective accumulation of cGMP which is unaffected by epithelium removal. This is inhibited in a stereoselective manner by L-NAME and mimicked by SNP and SIN-1; however, cGMP accumulation was greatly increased with SNP and SIN-1 suggesting compartmentalized changes in cGMP content. VIP also caused relaxation associated with an increase of cAMP; however, no evidence was found for VIP being involved in i-NANC relaxation. Hence nitric oxide (NO), or a NO-containing complex, appears to mediate i-NANC responses in human trachea in vitro.
 ...
PMID:Evidence for the involvement of cGMP in neural bronchodilator responses in humal trachea. 765 Jun 19

NG-nitro-L-arginine methyl ester (L-NAME, 400-1500 micrograms), administered intrathecally (ith.), elicits a slight but dose-related antinociception in rats, assessed by tail-flick and paw pressure tests. L-NAME (400 micrograms) and morphine (0.5 microgram) coadministered ith. elicit a profound and long-lasting antinociception, which is abolished by ith. administration of 3-morpholino-sydnonimine (SIN-1, 100 micrograms). Hemoglobin (266 micrograms) administered ith. also slightly potentiates morphine antinociception. These results suggest that nitric oxide (NO) is involved in spinal nociceptive events, and that the increased production of NO following the nociceptive input may diminish the efficiency of opioid antinociception in the spinal cord.
 ...
PMID:Inhibition of nitric oxide synthase enhances morphine antinociception in the rat spinal cord. 768 46

1. The effects of hydrogen peroxide (H2O2, 0.1-1 mM) on the tone of the rings of rabbit aorta precontracted with phenylephrine (0.2-0.3 microM) were studied. 2. H2O2 induced a concentration-dependent relaxation of both the intact and endothelium-denuded rings. However, in the presence of intact endothelium, H2O2-induced responses were 2-3 fold larger than in its absence, demonstrating the existence of endothelium-independent and endothelium-dependent components of the vasorelaxant action of H2O2. 3. The endothelium-dependent component of H2O2-induced relaxation was prevented by NG-nitro-L-arginine methyl ester (L-NAME, 30 microM) or NG-monomethyl-L-arginine (300 microM), inhibitors of nitric oxide synthase (NOS), in a manner that was reversible by L-, but not by D-arginine (2mM). The inhibitors of NOS did not affect the responses of denuded rings. 4. Methylene blue (10 microM), an inhibitor of soluble guanylate cyclase, blocked H2O2-induced relaxation of both the intact and denuded rings. 5. H2O2 (1 mM) enhanced the efflux of cyclic GMP from both the endothelium-intact and denuded rings. The effect of H2O2 was 4 fold greater in the presence of intact endothelium and this endothelium-dependent component was abolished after the inhibition of NOS by L-NAME (30 microM). 6. In contrast to the effects of H2O2, the vasorelaxant action of stable organic peroxides, tert-butyl hydroperoxide or cumene hydroperoxide, did not have an endothelium-dependent component. Moreover, they did not potentiate the efflux of cyclic GMP from the rings of rabbit aorta. 7. Exogenous donors of NO, specifically, 3-morpholinosydnonimine (SIN-1), glyceryl trinitrate or sodium nitroprusside were used to decrease the tone of denuded rings to the level induced by endogenous NO released from intact endothelium. This procedure did not influence the vasorelaxant activity of H202, showing that H202 does not potentiate the vasorelaxant action of NO within the smooth muscle.8. Thus, H202-induced relaxation in the rabbit aorta has both endothelium-dependent and independent components. The endothelium-dependent component of the relaxant action of H202 is due to enhanced endothelial synthesis of NO.
 ...
PMID:Involvement of nitric oxide in the endothelium-dependent relaxation induced by hydrogen peroxide in the rabbit aorta. 769 74

The aim of the present study was to investigate, whether nitric oxide (NO) modifies prostacyclin synthesis in endothelial cells. Two different NO-donors: SIN-1 (3-morpholino sydnonimine) and GEA 3175 (4-aryl-substituted oxatriazol derivative), and the NO-synthesis inhibitor; L-NAME were used. Endothelial cells were incubated with the tested compounds with or without Ca ionophore A23187 stimulation. SIN-1 (> 33 microM) and GEA 3175 (> 1 microM) increased the endothelial cGMP levels independently of A23187 stimulation. SIN-1 did not influence prostacyclin synthesis. GEA 3175 (> 33 microM) increased prostacyclin synthesis up to 2-fold, when incubated without A23187. GEA 3175 with A23187 induced about 30% inhibition in prostacyclin synthesis. L-NAME decreased unstimulated prostacyclin synthesis and this inhibition was reversed by GEA 3175. Obviously NO is able to modulate prostacyclin synthesis, however, much higher concentrations are needed than those to increase cGMP synthesis.
 ...
PMID:Effects of NO-donors, SIN-1 and GEA 3175 on prostacyclin and cGMP synthesis in cultured rat endothelial cells. 771 80

The objective of this investigation was to determine the effect of cultured human umbilical vein endothelial cells (HUVEC) on the vascular response to canine coronary arteries in which the endothelium had been either mechanically removed or injured by multiple brief episodes of occlusion and reperfusion in vivo. The endothelium-dependent vasodilator, A23187 (10(-6) mol/l) did not cause any significant relaxation in vessels from which the endothelium had been removed. However, following addition of cultured HUVEC to the tissue bath (75 x 10(3) cells/ml), A23187 produced a significant (p < 0.05) relaxation. This effect was abolished by inhibition of nitric oxide synthase with Nw-nitro-l-arginine methyl ester (L-NAME). Vascular relaxation caused by the nitric oxide donor SIN-1 was significantly (p < 0.05) enhanced when cultured HUVEC were added to vessels mechanically denuded of endothelium. Repetitive ischemia and reperfusion significantly inhibited the relaxant response to A23187. Addition of cultured HUVEC to the tissue bath partially restored the response to A23187. In contrast to the mechanically damaged vessels the relaxant response to SIN-1 was unaffected by cultured HUVEC in reperfusion-injured vessels. These results demonstrate that cultured endothelial cells partially restore endothelium-dependent vasodilation of vessels in which the endothelium is not functional following mechanical- or reperfusion-induced damage. The differential effect of endothelial cells on the response to SIN-1 suggests that mechanical and reperfusion injury alter the coronary vascular response to SIN-1 by different mechanisms.
 ...
PMID:Cultured endothelial cells restore vasodilator responses to coronary arteries with impaired endothelial function and alter the response to a nitric oxide donor. 783 88

1. The effect on cyclic nucleotide contents of selective inhibitors of cyclic nucleotide phosphodiesterase (PDE) isoforms III and IV (respectively SK&F 94120 and rolipram) and their interactions with endothelium and NO have been studied in rat aorta in the presence of indomethacin (10 microM). The participation of NO was assessed by using either NG-nitro-L-arginine methyl ester (L-NAME) (NO synthase inhibitor: 30 microM) or 3-morpholinosydnonimine (SIN-1, NO donor: 10 microM with SOD 100 units ml-1). 2. The presence of endothelium significantly increased both adenosine 3':5'-cyclic monophosphate (cyclic AMP, 1.7 fold) and guanosine 3':5'-cyclic monophosphate (cyclic GMP, 2.2 fold) contents. Cyclic GMP was largely affected by L-NAME or SIN-1 treatment, this was not the case for cyclic AMP suggesting that the presence of endothelium modified cyclic AMP content in aorta independently of the NO production. 3. In the presence or absence of endothelium, neither SK&F 94120 nor rolipram, alone or combined, significantly modified cyclic GMP content. 4. The PDE III inhibitor significantly affected cyclic AMP content only in non treated aorta without endothelium. In contrast, the PDE IV inhibitor increased cyclic AMP in all conditions. These increases were generally about 2 fold but markedly higher in aorta treated with SIN-1 and superoxide dismutase (SOD, 6 fold). Association of a low concentration of the PDE III inhibitor (5 microM) with the PDE IV inhibitor (30 microM) potentiated the effect of the PDE IV inhibitor on cyclic AMP content, except for aorta without endothelium treated with SIN-1 plus SOD. 5. These data indicate that the presence of the endothelium could increase cyclic AMP content independently of NO and prostacyclin (PGI2) production. Furthermore, an increase in cyclic GMP content (modulated by NO production) could enhance the cyclic AMP accumulation induced by the PDE IV inhibitor. This result supports the hypothesis that PDE III inhibition by endogenous cyclic GMP may potentiate the effect of PDE IV inhibition on cyclic AMP content. Taken together with our previous studies on relaxation, these results suggest that the NO/cyclic GMP pathway could induce PDE IV-dependent regulation of cyclic AMP via PDE III inhibition.
 ...
PMID:Role of phosphodiesterases III and IV in the modulation of vascular cyclic AMP content by the NO/cyclic GMP pathway. 783 94

The respective effects of hyperosmolarity caused by impermeant solutes, such as mannitol and sucrose, on the endothelium and smooth muscles cell responses were investigated in the rat tail artery. The vessels, with or without endothelium, were infused and superfused with an isosmolar saline solution, and were repeatedly stimulated with phenylephrine. Superfusing with hyperosmolar fluid (390-420 mosm/l) produced a transient increase in the arterial basal perfusion pressure which peaked after approximately 5 min and then declined within 15 min to a stable nonsignificant value above control values in subsequent experiments. In arteries with functional endothelium, the effect of phenylephrine was about 1.9-fold larger in hyperosmotic medium compared to that in isosmotic medium. In hyperosmotic media the response was still more than twofold enhanced in endothelium-denuded vessels compared to those with endothelium. In the latter, indomethacin (10 microM) had no effect, but N omega-nitro-L-arginine methylester (L-NAME; 30 mumol/l), an inhibitor of NO production, enhanced the response to phenylephrine to reach the same magnitude of response as seen in endothelium-denuded arteries. This effect of L-NAME was antagonized by L-arginine. Relaxation induced by the NO donor SIN-1 was unchanged by hyperosmolarity, indicating that the effect of NO was not impaired. It is concluded that, in the rat tail artery, the enhancement in phenylephrine-induced contractions produced in a hyperosmolar solution is due to both an endothelium-independent increase in smooth muscle responses and a moderate decrease in the production of NO, or an NO-like factor, by the endothelium. In spite of this reduction, endothelium-derived NO still plays a major role in attenuating phenylephrine-induced contractions in hyperosmolar medium.
 ...
PMID:Hyperosmolarity enhances smooth muscle contractile responses to phenylephrine and partially impairs nitric oxide production in the rat tail artery. 787 11

Cholinergic modulation of heart rate in isolated spontaneously beating single cells from the rabbit sino-atrial node was investigated by measuring transmembrane ionic currents using the nystatin-perforated patch whole-cell voltage-clamp technique. Carbamylcholine (CCh), a stable analogue of acetylcholine (ACh), significantly inhibited L-type calcium currents (Ica(L) which had been augmented by beta-adrenergic stimulation. In addition, CCh activated a potassium outward current (IK(ACh)). Both effects were blocked by atropine. The possible involvement of nitric oxide (NO) in these responses was evaluated by inhibiting NO synthesis. In the presence of NG-monomethyl-L-arginine (L-NMMA, 100 microM) or nitro-L-arginine methyl ester (L-NAME, 1 mM), two specific inhibitors of nitric oxide synthase (NOS), CCh no longer inhibited ICa(L). IK(ACh) could still be activated. Co-incubation of cells in L-NAME or in L-NMMA with arginine (the endogenous substrate of NOS) restored the CCh-induced attenuation of ICa(L), indicating that L-NAME or L-NMMA did not interfere directly with the muscarinic action of CCh on ICa(L). Effects of the NO-releasing agent molsidomine (SIN-1) on CCh-induced changes in ICa(L) were also investigated. After ICa(L) had been augmented by beta-adrenergic stimulation, SIN-1 (0.1 mM) inhibited ICa(L); however, SIN-1 had no further inhibitory effect after a maximal CCh concentration had been applied. These findings suggest that NO generation is an obligatory process in cholinergic inhibition of ICa(L) in mammalian cardiac pacemaker tissue.
 ...
PMID:An obligatory role for nitric oxide in autonomic control of mammalian heart rate. 791 69

1. The effect of endogenous and exogenous nitric oxide on the membrane potential (Em) of smooth muscle cells of the thoracic aorta of rats was investigated. 2. In tissues with intact endothelium, application of ACh or carbachol generated a change of the membrane potential consisting of an initial hyperpolarization by 10-12 mV, followed by a partial recovery toward a level which was at 10 min still 6-8 mV more negative than in control conditions. 3. Application of NG-nitro-L-arginine methylester (L-NAME), an inhibitor of endogenous NO production, had no significant effect on the resting membrane potential. The initial peak endothelium-dependent hyperpolarization elicited by ACh or carbachol was not significantly diminished. However, the recovery was more accentuated. Similarly, NG-monomethyl-L-arginine (L-NMMA) significantly diminished the second component of the endothelium-dependent hyperpolarization without affecting the magnitude of the first transient peak Em change. 4. Nitroglycerin produced a small sustained hyperpolarization of 1-2 mV, and the NO donor SIN-1, the active metabolite of molsidomine, similarly increased Em by about 1 mV. Infusion of high doses of acidified NaNO2 solution caused a hyperpolarization smaller than that evoked by ACh or carbachol. 5. 8-Bromo-cyclic GMP caused little change of membrane potential. In the presence of 8-Br-cGMP, ACh evoked a membrane electrical response similar to that observed in the absence of the nucleotide. 6. It is concluded that, in the rat aorta, the initial peak endothelium-dependent hyperpolarization observed under the influence of ACh or carbachol is not directly related to the synthesis of NO.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Contribution of nitric oxide to the endothelium-dependent hyperpolarization in rat aorta. 802 34


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>