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)

Pithed rats were used to compare the abilities of vasopressin and NG-nitro-L-arginine methyl ester (L-NAME) to prevent the early (1 h after starting an endotoxin infusion) E. coli endotoxin-induced impairment of pressor responsiveness to noradrenaline, cirazoline, BHT 933 and to sympathetic stimulation (T8). L-NAME increased arterial blood pressure and augmented pressor responses to noradrenaline and to sympathetic nerve stimulation to a similar degree in control and endotoxin-treated rats. The response to the alpha 1-adrenoceptor agonist cirazoline was augmented by L-NAME in endotoxin-treated rats only, whereas the response to the alpha 2-adrenoceptor agonist BHT 933 was unaffected. Vasopressin (0.64 I.U. kg-1 h-1) prevented the hypotension that resulted from endotoxin administration and produced a similar increase in blood pressure to that produced by L-NAME. This dose of vasopressin also augmented pressor responses to noradrenaline and sympathetic nerve stimulation similarly in both control and endotoxin-treated rats. Sodium nitroprusside, in a dose that mimicked the degree of hypotension caused by endotoxin, also impaired pressor responsiveness to cirazoline; this impairment was prevented by co-infusion of vasopressin. Thus the effects of L-NAME in preventing the early phase of endotoxin-induced impairment of vascular responsiveness may be related to its hypertensive properties, due to inhibition of the constitutive form of nitric oxide synthase, rather than inhibition of endotoxin-induced nitric oxide synthase. These data suggest that early endotoxin-induced impairment of vascular reactivity probably involves factors other than nitric oxide. The well documented effect of endotoxin in inducing nitric oxide synthase probably explains the later, more sustained loss of vascular responsiveness.
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PMID:Modification of alpha-adrenoceptor-mediated pressor responses by NG-nitro-L-arginine methyl ester and vasopressin in endotoxin-treated pithed rats. 128 May 96

The present studies were performed in order to examine the possible role of cyclic GMP-stimulated phosphodiesterase (cGMP-PDE) activity in the inhibitory action of the inflammatory peptide bradykinin on cyclic AMP (cAMP) accumulation in D384 cells. Bradykinin decreased the forskolin-stimulated cAMP accumulation in the presence of the phosphodiesterase inhibitor rolipram, and caused a transient 50% rise in cellular cGMP in the presence of the nonselective PDE inhibitor 3-isobutyl-1-methylxanthine (IBMX). Both basal and bradykinin-stimulated cGMP accumulation were about 8 times higher in the presence of IBMX than in the presence of rolipram. Sodium nitroprusside, which caused a 20-70-fold increase in cGMP levels reduced forskolin stimulated cAMP accumulation, whereas hydroxylamine, which maximally caused a 16-fold increase in cGMP, did not. 8-bromo-cGMP or dibutyryl cGMP had no effect on cAMP accumulation induced by forskolin. The inhibitory effect of nitroprusside was totally reversed by blocking the soluble guanylate cyclase activity by methylene blue treatment; however, the inhibitory action of bradykinin on cAMP accumulation was not changed by this treatment. Additionally, inhibition of nitric oxide synthesis, which is known to be regulated by Ca2+ and in turn stimulates cGMP production, by N omega-nitro-L-arginine (L-NAME) treatment did not alter the inhibitory effect of bradykinin on forskolin-induced cAMP accumulation. These results indicate that large increases in cGMP may regulate cAMP via cGMP-PDE whereas the small increase induced by bradykinin is insufficient and that cGMP is not involved in the inhibitory action of bradykinin on cAMP levels in D384 cells.
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PMID:Bradykinin inhibition of cyclic AMP accumulation in D384 astrocytoma cells. Evidence against a role of cyclic GMP. 128 20

Antropyloroduodenal motility was recorded in seven anesthetized dogs to assess the role of nitric oxide and L-arginine metabolites in nonadrenergic noncholinergic (NANC) mediation of pyloric relaxation. Pyloric activity induced by duodenal field stimulation was inhibited by antral field stimulation and electrical vagal stimulation. Intra-arterial NG-L-arginine-methyl-ester (L-NAME) reduced the inhibition from antral or vagal stimulation (P less than 0.05). Intravenous infusion of L-NAME also blocked the inhibitory effect of vagal and antral stimulation but left the tetrodotoxin-insensitive action of intra-arterial vasoactive intestinal peptide (VIP) and sodium nitroprusside unchanged. L-Arginine reversed the effect of L-NAME whereas D-arginine did not. L-NAME enhanced pyloric contractions to intra-arterial acetylcholine. The NANC inhibition of the substance P-stimulated pyloric response in vitro was blocked by L-NAME and reversed by addition of L-arginine. Sodium nitroprusside was effective as a relaxant in vitro but VIP was not. These data suggest that metabolites of L-arginine mediate neural inhibition of canine pyloric motor activity.
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PMID:Nitric oxide as a putative nonadrenergic noncholinergic inhibitory transmitter in the canine pylorus in vivo. 134 7

1. We have used an isolated, buffer-perfused, rabbit ear model of acute arterial occlusion to investigate the effects of the nitrovasodilator sodium nitroprusside, the potassium channel activator BRL 38227 (the active (-)-enantiomer of cromakalim) and the calcium antagonist, verapamil, on collateral perfusion in the absence of pharmacological tone. 2. Verapamil was the most potent vasodilator (EC50 = 72.6 +/- 32.0 nM) of 5-hydroxytryptamine/histamine-induced tone in the rabbit isolated perfused ear. Sodium nitroprusside and BRL 38227 were less potent with respective EC50 values of 488 +/- 75 nM and 296 +/- 40 nM. Following inhibition of endothelium-derived relaxing factor (EDRF) synthesis, the potency of BRL 38227 was significantly (P less than 0.001) increased with an EC50 of 55.6 +/- 5.0 nM. 3. BRL 38227 at 500 nM and 3 microM induced substantial increases in collateral perfusion following arterial ligation in the absence of pharmacological tone compared to control. Furthermore 3 microM BRL 38227 completely reversed the attenuation of collateral perfusion which followed inhibition of EDRF synthesis with 100 microM NG-nitro-L-arginine methyl ester (L-NAME). 4. Sodium nitroprusside (500 nM and 3 microM) induced modest improvements in collateral perfusion in the early stages after arterial occlusion. 5. Verapamil did not influence collateral perfusion at either of the concentrations used (50 nM and 3 microM), even though it was a potent vasodilator. 6. The results of this study indicate that BRL 38227, and to a much lesser extent sodium nitroprusside, selectively improve collateral perfusion following arterial occlusion, even in the presence of effects of EDRF on acute collateralization, while verapamil has no effect. Furthermore, BRL 38227 also improves collateral perfusion following inhibition of EDRF synthesis. It remains to be established whether BRL 38227 has beneficial actions in acute arterial occlusion in vivo.
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PMID:Effects of BRL 38227, sodium nitroprusside and verapamil on collateral perfusion following acute arterial occlusion in the rabbit isolated ear. 139 64

This study provides mechanical and electrophysiological evidence to show that a metabolite of arginine, not vasoactive intestinal peptide (VIP), is the putative nonadrenergic noncholinergic (NANC) inhibitory mediator in canine and opossum lower esophageal sphincters (LES). Relaxations of spontaneous active tension by electrical field stimulation (FS) at parameters that induced tetrodotoxin (TTX)-sensitive responses were abolished by L-N omega-arginine methyl ester (L-NAME) at 10(-4) M and restored by L-arginine (10(-3) M) but not D-arginine (10(-3) M). TTX-insensitive relaxations to 5-ms pulses were unaffected by L-NAME, L- or D-arginine. VIP (10(-6) M) caused maximum relaxations of basal tension in both the opossum and canine LES. However these relaxations, unlike those from FS were unaffected by L-NAME. Methylene blue (5 x 10(-5)M) increased basal tension of the LES in each species, and did not inhibit the relaxation to FS or VIP, but often increased the amplitudes of these responses due to the increase in basal tension. In parallel experiments NANC inhibition of body circular muscle from opossum esophagus was abolished by methylene blue. Electrophysiological studies using micro-electrodes revealed that NANC inhibition was associated with inhibitory junction potentials in the canine LES. These were inhibited by L-NAME and restored by L-arginine but not D-arginine. In contrast, 10(-6) M VIP in canine LES did not induce any change in membrane potential during a 20-min superfusion. Sodium nitroprusside also hyperpolarized sphincteric muscle and its effects were not affected by L-NAME.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A mediator derived from arginine mediates inhibitory junction potentials and relaxations in lower esophageal sphincter: an independent role for vasoactive intestinal peptide. 147 49

The effects of the sodium channel activators veratridine and batrachotoxin on isolated rat aorta were investigated. Veratridine caused gradual contraction, independent of the presence of endothelium, with an EC50 of 35 microM. Batrachotoxin (1 microM) also induced contraction. Both effects were completely inhibited by the sodium channel blocker tetrodotoxin (1 microM). The veratridine (60 microM)-induced contraction was inhibited by nifedipine (0.1 microM). In the absence of extracellular Ca2+, veratridine (60 microM) did not cause contraction. Sodium nitroprusside (80 nM), acetylcholine (10 microM) and isoproterenol (1 microM) caused relaxation of rings precontracted with veratridine (60 microM). An inhibitor of endothelium-derived relaxing factor (EDRF) synthase, N omega-nitro-L-arginine methyl ester (L-NAME) (0.65 mM), enhanced the veratridine-induced contraction in rings with an intact endothelium, which suggests that EDRF was being released during the veratridine-induced contraction. These results show that the activation of sodium channels on smooth muscle cells induces a contraction that is probably mediated by Ca2+ influx through voltage-dependent Ca2+ channels.
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PMID:Vascular smooth muscle contraction induced by Na+ channel activators, veratridine and batrachotoxin. 166 87

1. Conscious, Long Evans rats (n = 16), chronically instrumented for the measurement of regional haemodynamics were given 3 min, randomized infusions of two doses of sodium nitroprusside (1.5 and 15 micrograms min-1), acetylcholine (0.4 and 4 micrograms min-1), 5'-N-ethylcarboxamidoadenosine (NECA; 45 and 450 ng min-1), and salbutamol (24 and 240 ng min-1) in the absence and in the presence of NG-nitro-L-arginine methyl ester (L-NAME; 1 mg kg-1 h-1), a potent inhibitor of nitric oxide biosynthesis. 2. Sodium nitroprusside caused hyperaemic vasodilatation in the mesenteric, and common carotid vascular beds. These effects were enhanced in the presence of L-NAME, as was the hypotension. 3. Acetylcholine caused hyperaemic vasodilation inp6he renal, internal carotid and common carotid vascular beds. These effects were attenuated in the presence of L-NAME, but the hypotension was unaffected. 4. NECA caused hyperaemic vasodiltation in the renal, mesenteric, hindquarters, internal carotid and common carotid vascular beds. However, only the hindquarters and internal carotid responses were diminished in the presence of L-NAME and the hypotension was unchanged. 5. Salbutamol caused hyperaemic vasodilatation in the hindquarters vascular bed only. This effect was reduced in the presence of L-NAME, but the hypotension was unchanged. 6. The results indicate marked regional variations in the sensitivity of vasodilator responses to L-NAME that can depend on the vasodilator agent chosen and the dose employed. It is clear from these findings also that measurement of mean arterial blood pressure alone cannot provide adequate information on which to judge the involvement of L-NAME-sensitive mechanisms in vasodilator responses in vivo.
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PMID:Effects of NG-nitro-L-arginine methyl ester on vasodilator responses to acetylcholine, 5'-N-ethylcarboxamidoadenosine or salbutamol in conscious rats. 193 36

The effects of N-omega-nitro-L-arginine methyl ester (L-NAME) on basal cerebral vascular tone, the vasodilatory effects of acetylcholine (ACh), and the cerebrovascular response to alterations in arterial carbon dioxide tension (CBVR) were investigated using near-infrared spectroscopy. Seven newborn piglets were anesthetized and mechanically ventilated; mean arterial blood pressure (MAP) was monitored and near-infrared spectroscopy used to measure changes in total cerebral Hb concentration. At the beginning of the experiment, CBVR was measured and then 10, 20, 30, and 100 mg.kg-1 L-NAME were administered sequentially; ACh (1, 2, 3, and 5 micrograms) was given before and after each injection of L-NAME. At the end of this sequence, CBVR was measured again and finally sodium nitroprusside (1.5 mg.kg-1) was administered. Ten and 20 mg.kg-1 L-NAME caused a significant decrease in total cerebral Hb concentration of -0.59 (-3.21 to -0.02) and -1.46 (-6.50 to -0.15) mumol.L-1 (median and range), respectively (Wilcoxon p < 0.05), but subsequent injections did not. Ten, 20, and 100 mg.kg-1 L-NAME caused an increase in MAP (Wilcoxon p < 0.05). ACh caused an increase in total cerebral Hb concentration and a decrease in MAP that was impaired but not abolished by L-NAME (ANOVA p < 0.05). CBVR was not affected by L-NAME. Sodium nitroprusside caused a reduction in mean (SD) MAP of 4.7 (1.6) kPa, and a slower rise in [tHb] of 13.44 (2.03) mumol.L-1. Postmortem examination of three animals revealed NADPH-diaphorase staining in neurons, cerebral blood vessels, carotid artery, and jugular vein.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of N-omega-nitro-L-arginine methyl ester on the cerebral circulation of newborn piglets quantified in vivo by near-infrared spectroscopy. 751 Aug 71

1. The involvement of nitric oxide (NO) in the regulation of angiogenesis was examined in the in vivo system of the chorioallantoic membrane (CAM) of the chick embryo and in the matrigel tube formation assay. 2. Sodium nitroprusside (SNP) (0.37-28 nmol/disc), which releases NO spontaneously, caused a dose-dependent inhibition of angiogenesis in the CAM in vivo and reversed completely the angiogenic effects of alpha-thrombin (6.7 nmol/disc) and the protein kinase C (PKC) activator 4-beta-phorbol-12-myristate-13-acetate (PMA) (0.97 nmol/disc). In addition, SNP (28 x 10(-6) M) stimulated the release of guanosine 3'-5'-cyclic monophosphate (cyclic GMP) from the CAM in vitro. 3. In the matrigel tube formation assay, an in vitro assay of angiogenesis, both SNP (1-3 x 10(-6) M) and the cell permeable cyclic GMP analogue, Br-cGMP (0.3-1.0 x 10(-3) M) reduced tube formation. 4. The inhibitors of NO synthase, NG-monomethyl-L-arginine (L-NMMA) (3.8-102 nmol/disc) and NG-nitro-L-arginine methylester (L-NAME) (1.3-34.2 nmol/disc) stimulated angiogenesis in the CAM in vivo, in a dose-dependent fashion. D-NMMA and D-NAME on the other hand had no effect on angiogenesis in this system. 5. L-Arginine (10.9 nmol/disc), although it had a modest antiangiogenic effect by itself, was capable of abolishing the angiogenic effects of L-NMMA (34.2 nmol/disc) and of L-NAME (3.8 nmol/disc). 6. Dexamethasone, an inhibitor of the induction of NO synthase, at 0.2-116.1 nmol/disc, stimulated angiogenesis in the CAM, whereas at 348.4-1161 nmol/disc it inhibited this process. Combination of 38.7 nmol/disc dexamethasone with L-NAME (9.3 nmol/disc) resulted in a potentiation of the angiogenic effect of the former. It appears therefore that both the constitutive and the inducible NO synthase may contribute to the NO-mediated inhibition of angiogenesis. 7. Superoxide dismutase (SOD), which prevents the destruction of NO, at 300 i.u./disc had a modest antiangiogenic effect in the CAM, by itself. In addition, SOD, prevented alpha-thrombin (6.7 nmol/disc) and PMA (0.97 nmol/disc) from stimulating angiogenesis in the CAM.8. These results suggest that NO may be an endogenous antiangiogenic molecule of pathophysiological importance.
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PMID:Evidence that nitric oxide is an endogenous antiangiogenic mediator. 751 30

1. We have examined the effects of nitric oxide inhibition, indomethacin and the dual lipoxygenase/cyclo-oxygenase inhibitor, 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW755C), on the responses of small mesenteric arteries of Wistar rats, with and without endothelium, to noradrenaline, potassium chloride, endothelin-1, acetylcholine and sodium nitroprusside. 2. Noradrenaline, potassium chloride and endothelin-1 caused concentration-dependent contraction of small mesenteric arteries. Indomethacin (14 microM) attenuated the contractile response to both noradrenaline and potassium chloride. The inhibitory action of indomethacin persisted in vessels treated with CHAPS. 3. Acetylcholine produced concentration-dependent relaxation in these vessels. Indomethacin (14 microM) had no significant effect on the acetylcholine concentration-response relationship. 4. NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) potentiated the contractile response to both noradrenaline and potassium chloride and inhibited acetylcholine-induced relaxation. Indomethacin attenuated the effects of L-NAME. 5. BW755C inhibited the contractile response to noradrenaline and potassium chloride but not to endothelin-1. The inhibitory effects of BW755C persisted in the presence of indomethacin and in vessels treated with CHAPS. 6. BW755C enhanced endothelium-dependent relaxation, as assessed by the response to acetylcholine. In the presence of indomethacin, BW755C produced a shift to the right of the concentration-response curve to acetylcholine. 7. Inhibition of nitric oxide synthase with L-NAME, reversed the inhibitory effect of BW755C on noradrenaline- and potassium-induced contraction. L-NAME and BW755C in combination resulted in a shift to the right of the concentration-response curve to acetylcholine. 8. Sodium nitroprusside produced concentration-dependent relaxation of the vessels. Endothelium removal reduced the maximum relaxation to nitroprusside. BW755C did not alter the response to sodium nitroprusside in vessels with or without endothelium.9 .These data support the existence of two vasoconstrictor products of arachidonic acid released during contraction of small mesenteric arteries with noradrenaline and potassium chloride: a cyclo-oxygenase product and a lipoxygenase product both of which appear to be largely endothelium-independent.
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PMID:Interdependence of contractile responses of rat small mesenteric arteries on nitric oxide and cyclo-oxygenase and lipoxygenase products of arachidonic acid. 752 Dec 54

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