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)

1. The possible roles of the L-arginine-NO pathway and of guanosine 3':5'-cyclic monophosphate (cyclic GMP) in regulating the prejunctional release of noradrenaline and neurogenic vasoconstriction were investigated in the perfused rat tail artery. 2. In the presence of N omega-nitro-L-arginine methyl ester (L-NAME; 30 microM), an inhibitor of NO formation, the vasoconstrictor responses to perivascular nerve stimulation (24 pulses at 0.4 Hz, 0.3 ms, 200 mA) and to exogenous noradrenaline (1 microM) were significantly enhanced, whereas the stimulation-evoked tritium overflow from [3H]-noradrenaline preloaded arteries was not modified. The vasoconstriction enhancing effect of L-NAME was prevented by L-arginine (1 mM) but not D-arginine (1 mM) and was abolished by removal of the endothelium. 3. The NO donor, 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1; 0.1-30 microM), and the cyclic GMP phosphodiesterase inhibitor, zaprinast (0.1-30 microM) both induced a concentration-dependent inhibition of the electrical field stimulation-induced vasoconstriction, while atrial natriuretic peptide (ANP; 100 nM) produced only a slight decrease of the vasoconstrictor response. Methylene blue (3 microM), a known inhibitor of soluble guanylate cyclase increased the electrical field stimulation-induced vasoconstriction. SIN-1 and methylene blue when administered simultaneously, antagonized each others effect. None of the compounds tested (SIN-1, zaprinast, ANP or methylene blue) had any significant effect on the stimulation-evoked [3H]-noradrenaline overflow. 4. 8-Bromo-cyclic GMP, a potent activator of cyclic GMP-dependent protein kinase, markedly and concentration-dependently (3-300 microM) increased [3H]-noradrenaline overflow but decreased field stimulation-induced vasoconstriction. Dibutyryl-cyclic GMP (100 JM), a weak activator of cyclic GMP-dependent protein kinase, affected neither the pre- nor the postjunctional response to electrical field stimulation.5. These data show that an NO-like substance of endothelial origin, derived from L-arginine, attenuates vasoconstriction in the rat tail artery, whether neurally-induced or evoked by exogenous noradrenaline.Since noradrenaline release was unaltered by compounds modifying NO production, this NO-like compound acted through a postjunctional mechanism. The lack of prejunctional effects of both soluble and membrane-associated guanylate cyclase activators, despite a large effect of 8-bromo-cyclic GMP,suggests that endogenous cyclic GMP production, if present in sympathetic nerves, may not be involved in the regulation of noradrenaline release in the rat tail artery.
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PMID:Role of the L-arginine-NO pathway and of cyclic GMP in electrical field-induced noradrenaline release and vasoconstriction in the rat tail artery. 133 57

1. The present study was performed to investigate how blockade of the L-arginine/nitric oxide (NO) pathway influences the function of the lower urinary tract in vivo, as studied by cystometry in conscious rats and in vitro, in isolated muscle preparations from the rat detrusor and urethra. 2. L-NG-nitro arginine methyl ester (L-NAME), 10 and 20 mg kg-1, administered intra-arterially, decreased micturition volume and bladder capacity, and increased spontaneous bladder contractions. D-NAME (20 mg kg-1) had no effect. No changes in the urodynamic parameters were recorded if L-NAME (20 mg kg-1) was administered in combination with L-arginine (200 mg kg-1). 3. Cystometries performed after intra-arterial administration of sodium nitroprusside (SNP) (3 mg kg-1) and 3-morpholino-sydnonimin hydrochloride (SIN-1, 2 mg kg-1) showed a decrease in bladder capacity, micturition volume and threshold pressure. SIN-1, but not SNP, induced spontaneous bladder contractions. 4. Isolated precontracted urethral preparations responded to electrical stimulation with a frequency-dependent tetrodotoxin-sensitive relaxation. L-NAME (10(-4) M), but not D-NAME, reduced the maximal relaxation to 31 +/- 8% (n = 8) of the response prior to drug administration. The inhibition induced by L-NAME was completely reversed by L-arginine (10(-3) M). SNP (10(-8)-10(-4) M), SIN-1 (10(-6)-3 x 10(-4) M) and NO (10(-5)-10(-3) M; present in acidified solution of NaNO2), caused relaxation (93-100%) of urethral preparations. L-NAME did not affect these relaxations.5. Detrusor strips contracted by carbachol or K' showed contractions in response to electrical stimulation, even when pretreated with a,p-methylene ATP and/or atropine. Small relaxations (14-41%) of detrusor strips were evoked by SNP (10-6-10-4M), SIN-1 (10-5-3 x 10-4M) and NO (10-5-10-3M). Electrically (20 Hz) induced contractions of the detrusor muscle were unaffected by addition of L-NAME (10-6_10-4 M) or L-arginine (10-3 M).6. The present results suggest that the L-arginine/NO pathway is of functional importance for the bladder outlet region, but that its role in the detrusor is questionable. They also suggest that the site of action of L-NAME for inducing bladder hyperactivity in the rat is the outlet region rather than the detrusor muscle.
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PMID:Effects of inhibition of the L-arginine/nitric oxide pathway in the rat lower urinary tract in vivo and in vitro. 142 71

Vascular endothelial cells synthesize nitric oxide from L-arginine, and this pathway can be inhibited by various analogues of L-arginine, including NG-nitro L-arginine methyl ester (L-NAME). To investigate the role of this pathway in the regulation of femoral arterial tone, the effect of L-NAME was studied in vitro in isolated canine femoral arteries suspended in organ chambers for isometric tension recording, and in vivo in conscious dogs chronically instrumented for the measurement of iliac blood flow and iliac artery diameter. In vitro, L-NAME induced an endothelium-dependent contraction, inhibited the endothelium-dependent relaxations to acetylcholine or bradykinin, and potentiated the relaxation evoked by the nitric oxide donor SIN-1. In vivo, locally administered L-NAME induced a decrease in iliac artery diameter and an increase in iliac resistance, potentiated the iliac responses to the organic nitrate nitroglycerin, but did not affect the iliac responses to the endothelium dependent vasodilator acetylcholine. Thus, in the canine femoral vascular bed: a) basal release of nitric oxide contributes in vivo to the maintenance of a permanent vasodilator tone at the level of both large conductance and small resistance vessels; b) the endothelium-dependent relaxations to acetylcholine and bradykinin in vitro are mostly mediated through the release of nitric oxide from L-arginine; c) the endothelium-dependent relaxations to acetylcholine in vivo are probably mediated by a relaxing factor distinct from nitric oxide, or by a nitric oxide-like molecule released from endothelial pools; and d) removal of the NO-mediated vasodilator tone by L-NAME leads to a supersensitivity to nitrovasodilators, both in vitro and in vivo.
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PMID:The L-arginine-nitric oxide pathway in the canine femoral vascular bed: in vitro and in vivo experiments. 179 33

The biochemical signaling pathways involved in nitric oxide (NO)-mediated cholinergic inhibition of L-type Ca2+ current (ICa[L]) were investigated in isolated primary pacemaker cells from the rabbit sinoatrial node (SAN) using the nystatin-perforated whole-cell voltage clamp technique. Carbamylcholine (CCh; 1 microM), a stable analogue of acetylcholine, significantly inhibited ICa(L) after it had been augmented by isoproterenol (ISO; 1 microM). CCh also activated an outward K+ current, IK(ACh). Both of these effects of CCh were blocked completely by atropine. Preincubation of the SAN cells with L-nitro-arginine methyl ester (L-NAME; 0.2-1 mM), which inhibits NO synthase (NOS), abolished the CCh-induced attenuation of ICa(L) but had no effect on IK(ACh). Coincubation of cells with both L-NAME and the endogenous substrate of NOS, L-arginine (1 nM), restored the CCh-induced attenuation of ICa(L), indicating that L-NAME did not directly interfere with the muscarinic action of CCh on ICa(L). In the presence of ISO the CCh-induced inhibition of ICa(L) could be mimicked by the NO donor 3-morpholino-sydnonimine (SIN-1; 0.1 mM). SIN-1 had no effect on its own or after a maximal effect of CCh had developed, indicating that it does not inhibit ICa(L) directly. SIN-1 failed to activate IK(ACh), demonstrating that it did not activate muscarinic receptors. Both CCh and NO are known to activate guanylyl cyclase and elevate intracellular cGMP. External application of methylene blue (10 microM), which interferes with the ability of NO to activate guanylyl cyclase, blocked the CCh-induced attenuation of ICa(L). However, it also blocked the activation of IK(ACh), suggesting an additional effect on muscarinic receptors or G proteins. To address this, a separate series of experiments was performed using conventional whole-cell recordings with methylene blue in the pipette. Under these conditions, the CCh-induced attenuation of ICa(L) was blocked, but the activation of IK(ACh) was still observed. Methylene blue also blocked the SIN-1-induced decrease in ICa(L). 6-anilino-5,8-quinolinedione (LY83583; 30 microM), an agent known to decrease both basal and CCh-stimulated cGMP levels, prevented the inhibitory effects of both CCh and SIN-1 on ICa(L), but had no effect on the activation of IK(ACh) by CCh. In combination, these results show that CCh- and NO-induced inhibition of ICa(L) is mediated by cGMP.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:A cellular mechanism for nitric oxide-mediated cholinergic control of mammalian heart rate. 749 38

Left lung autotransplantation (LLA) increased the pulmonary vasoconstriction evoked by phenylephrine and attenuated the vasodilatation caused by acetylcholine or bradykinin in conscious dogs. To study the mechanisms responsible for these changes, pulmonary arterial rings were isolated from right (control) and left (LLA) lower lobes of dogs 1-26 mo after LLA and were suspended for isometric tension recording. Compared with control rings from the same anatomic location, contractions to phenylephrine were increased after LLA in rings with or without endothelium. In arterial rings contracted to 50% of their maximal response to phenylephrine, acetylcholine, bradykinin, and calcium ionophore caused endothelium-dependent relaxations that were reduced in LLA compared with control rings. In arterial rings from control and LLA lungs, relaxations to acetylcholine were not altered by inhibition of cyclooxygenase (indomethacin) but were reduced after inhibition of NO synthase [N omega-nitro-L-arginine methyl ester (L-NAME)]. After L-NAME, there was no longer any significant difference in acetylcholine-induced relaxation between arterial rings from control and LLA lungs. Relaxation to SIN-1, a NO donor, was similar in arterial rings (without endothelium) from control and LLA lungs. The results suggest that LLA causes an increased sensitivity of vascular smooth muscle to alpha 1-adrenergic activation and endothelial dysfunction that is mediated by a selective reduction in the activity of endothelium-derived relaxing factor/NO.
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PMID:Endothelial and vascular smooth muscle responses are altered after left lung autotransplantation. 751 88

The present study aims at investigating the effect of pharmacological manipulation of nitric oxides (NOs) formation in the rat neurohypophysis on the secretion of vasopressin (AVP). We found that the NO synthase antagonist L-NAME and free-ferrous hemoglobin (an NO inactivator) produced a transient and significant enhancement of basal secretion of AVP from incubated glands. Conversely, the NO precursor L-arginine (but not its inactive counterpart D-arginine) antagonized the stimulatory influence of L-NAME on both AVP and oxytocin (OT) output. Elevation of NOs formation triggered by means of the NO donor SIN-1 likewise dampened spontaneous, as well as stimulated, AVP release. It is concluded that NOs molecules show up as potent regulators of neuropeptide secretion at the level of nerve terminals in the neurohypophysis.
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PMID:Evidence for an inhibitory effect of nitric oxides on neuropeptide secretion from isolated neural lobe of the rat pituitary gland. 751 25

We sought to determine whether the attenuation of the hypercapnic cerebrovasodilation associated with inhibition of nitric oxide synthase (NOS) can be reversed by exogenous NO. Rats were anesthetized (halothane) and ventilated. Neocortical cerebral blood flow (CBF) was monitored by a laser-Doppler probe. The NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME; 40 mg/kg iv) reduced resting CBF [-36 +/- 5% (SE); P < 0.01, analysis of variance] and attenuated the increase in CBF elicited by hypercapnia (partial pressure of CO2 = 50-60 mmHg) by 66% (P < 0.01). L-NAME reduced forebrain NOS catalytic activity by 64 +/- 3% (n = 10; P < 0.001). After L-NAME, intracarotid infusion of the NO donor 3-morpholinosydnonimine (SIN-1; n = 6) increased resting CBF and reestablished the CBF increase elicited by hypercapnia (P > 0.05 from before L-NAME). Similarly, infusion of the guanosine 3',5'-cyclic monophosphate (cGMP) analogue 8-bromo-cGMP (n = 6) reversed the L-NAME-induced attenuation of the hypercapnic cerebrovasodilation. The NO-independent vasodilator papaverine (n = 6) increased resting CBF but did not reverse the attenuation of the CO2 response. SIN-1 did not affect the attenuation of the CO2 response induced by indomethacin (n = 6). The observation that NO donors reverse the L-NAME-induced attenuation of the CO2 response suggests that a basal level of NO is required for the vasodilation to occur. The findings are consistent with the hypothesis that NO is not the final mediator of smooth muscle relaxation in hypercapnia.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:SIN-1 reverses attenuation of hypercapnic cerebrovasodilation by nitric oxide synthase inhibitors. 751 10

Since dietary salt loading enhances nitric oxide (NO) generation in the kidney, we investigated the hypothesis that changes in salt intake have specific effects on vascular resistance in the kidney mediated by the L-arginine-NO pathway. We contrasted changes in renal and hindquarter vascular resistances (RVR and HQVR) in anesthetized rats during intravenous infusions of graded doses of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Groups (N = 8 to 10) of rats were maintained on a high salt (HS) or low salt (LS) diet for two weeks. Compared to those on LS, rats on HS had a greater increase in mean arterial pressure (delta MAP; +32 +/- 4 vs. +22 +/- 3%; P = 0.05) and RVR (+160 +/- 17 vs. +83 +/- 10%; P < 0.005) and a greater fall in renal blood flow (delta RBF; -47 +/- 3 vs. -32 +/- 4%; P < 0.01); changes in HQVR were similar in the two groups. The enhanced RVR response to L-NAME in HS rats could not be ascribed to the higher renal perfusion pressure (RPP) since it persisted in rats whose RPP was controlled by adjustment of a suprarenal aortic clamp. Changes in RVR with an NO donor (SIN-1) were similar in HS and LS rats. L-NAME reduced plasma renin activity in both HS and LS rats. After inhibition of ACE with captopril, or of angiotensin II type I (AT1) receptor with losartan, the increase in RVR with L-NAME remained greater in HS than LS rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal vasoconstriction during inhibition of NO synthase: effects of dietary salt. 752 72

1. Recent studies have suggested that the generation of nitric oxide (NO) and hydrogen peroxide (H2O2) by islet NO synthase and monoamine oxidase, respectively, may have a regulatory influence on insulin secretory processes. We have investigated the pattern of insulin release from isolated islets of Langerhans in the presence of various pharmacological agents known to perturb the intracellular levels of NO and the oxidation state of SH-groups. 2. The NO synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME) dose-dependently increased L-arginine-induced insulin release. D-Arginine did not influence L-arginine-induced insulin secretion. However, D-NAME which reportedly has no inhibitory action on NO synthase, modestly increased L-arginine-induced insulin release, but was less effective than L-NAME. High concentrations (10 mM) of D-arginine as well as L-NAME and D-NAME could enhance basal insulin release. 3. The intracellular NO donor, hydroxylamine, dose-dependently inhibited insulin secretion induced by L-arginine and L-arginine+L-NAME. 4. Glucose-induced insulin release was increased by NO synthase inhibition (L-NAME) and inhibited by the intracellular NO donor, hydroxylamine. Sydnonimine-1 (SIN-1), an extracellular donor of NO and superoxide, induced a modest suppression of glucose-stimulated insulin release. SIN-1 did not influence insulin secretion induced by L-arginine or the adenylate cyclase activator, forskolin. 5. The intracellular 'hydroperoxide donor' tert-butylhydroperoxide in the concentration range of 0.03-3 mM inhibited insulin release stimulated by the nutrient secretagogues glucose and L-arginine. Low concentrations (0.03-30 microM) of tert-butylhydroperoxide, however enhanced insulin secretion induced by the phosphodiesterase inhibitor isobutylmethylxanthine (IBMX). 6. Islet guanosine 3':5'-cyclic monophosphate (cyclic GMP) content was not influenced by 10 mML-arginine or tert-butylhydroperoxide at 3 or 300 micro M but was markedly increased (14 fold) by a high hydroxylamine concentration (300 micro M). In contrast, islet adenosine 3':5'-cyclic monophosphate (cyclicAMP) content was increased (3 fold) by L-arginine (10 mM) and (2 fold) by tert-butylhydroperoxide(300 micro M).7. Our results strongly suggest that NO is a negative modulator of insulin release induced by the nutrient secretagogues L-arginine and glucose. This effect is probably not mediated to any major extent by the guanylate cyclase-cyclic GMP system but may rather be exerted by the S-nitrosylation of critical thiol groups involved in the secretory process. Similarly the inhibitory effect of tert-butylhydroperoxide is likely to be elicited through affecting critical thiol groups. The mechanism underlying the secretion promoting action of tert-butylhydroperoxide on IBMX-induced insulin release is probably linked to intracellular Ca2+-perturbations affecting exocytosis.8. Taken together with previous data the present results suggest that islet production of low physiological levels of free radicals such as NO and H202 may serve as important modulators of insulin secretory processes.
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PMID:Influence of nitric oxide synthase inhibition, nitric oxide and hydroperoxide on insulin release induced by various secretagogues. 753 13

1. Modulation of prostaglandin biosynthesis in vivo by either exogenous or endogenous nitric oxide (NO) has been studied in the rat using arachidonic acid (AA)-induced paw oedema and measuring both the foot volume and the amount of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha), the stable metabolite of prostacyclin (PGI2), in the oedematous fluid recovered from inflamed paws. 2. Paw injections of 150 or 300 nmol of AA were virtually inactive whereas 600 nmol produced a moderate oedema which was greatly reduced by the NO synthase inhibitor L-NG-nitro arginine methyl ester (L-NAME, 100 nmol/paw) and the NO scavenger haemoglobin (Hb, 30 mumol/paw), but unaffected by the inhibitor of the soluble guanylate cyclase, methylene blue (Mb, 3 mumol/paw) and L-arginine (15 mumol/paw). 3. The NO-donors (10 mumol/paw) 3-morpholino-sydnonimine-hydrochloride (SIN-1), S-nitroso-N-acetyl-D, L-penicillamine (SNAP) and sodium nitroprusside (SNP) significantly potentiated the paw oedema induced by AA (300 nmol/paw). 4. SIN-1 (2.5, 5 and 10 mumol/paw) produced a significant dose-dependent increase of the oedema induced by AA which was correlated with increased amounts of 6-keto-PGF1 alpha in the fluid recovered from inflamed paws. 5. Both oedema and prostaglandin biosynthesis induced by the combination AA+SIN-1 were greatly suppressed by either Hb (30 mumol/paw) or indomethacin (3 mumol/paw or 5 mg kg-1 s.c.) but unaffected by Mb (3 mumol/paw). 6. In LPS-treated rats (6 mg kg-1, i.p.) doses of AA inactive in normal animals produced a remarkable oedema which was reduced by L-NAME or Hb, unaffected by Mb and increased by L-arginine.7. These results demonstrate that NO increases prostaglandin biosynthesis in vivo through a guanosine 3': 5'-cyclic monophosphate (cyclic GMP)-independent mechanism and suggest that the interaction between NO synthase and cyclo-oxygenase (COX) pathways may represent an important mechanism for the modulation of the inflammatory response.
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PMID:Modulation by nitric oxide of prostaglandin biosynthesis in the rat. 753 14

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