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)

Vascular reactivity and activation of the nitric oxide (NO) pathway were investigated in perfused mesenteric vascular bed removed from rats 5 h after i.p. injection of bacterial lipopolysaccharide (E. coli lipopolysaccharide, 30 mg kg -1). Lipopolysaccharide treatment induced hyporesponsiveness to noradrenaline. Maximal noradrenaline-induced vasoconstriction was significantly reduced in lipopolysaccharide-treated vs. untreated preparations. Continuous infusion of L-arginine (L-Arg) (0.2 mM) enhanced noradrenaline hyporeactivity of lipopolysaccharide-treated rats. N omega-Nitro-L-arginine methyl ester (L-NAME) (0.2 mM), a non-selective inhibitor of NO synthase, failed to completely restore the noradrenaline hyporeactivity of lipopolysaccharide-treated + L-Arg-infused mesenteric vascular bed. After L-NAME treatment. Methylene blue (10 microM), a guanylate cyclase inhibitor, produced no additional increase of noradrenaline vasoconstriction in lipopolysaccharide-treated + L-Arg-infused mesenteric vascular bed, suggesting that an NO-independent activation of guanylate cyclase may be excluded. In lipopolysaccharide-treated preparations, L-Arg (0.2 mM) elicited a significant increase in nitrite production, which was antagonized by L-NAME. In conclusion, lipopolysaccharide-induced noradrenaline hyporesponsiveness of rat resistance vessels can only be partially explained by NO overproduction. Other mechanisms, probably related to vasoconstriction, may be involved.
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PMID:Hyporeactivity of mesenteric vascular bed in endotoxin-treated rats. 887 36

The effects of sodium nitroprusside (SNP) and acidified sodium nitrite (ASN) solutions, nitric oxide (NO)-donating compounds, and NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, were studied on the spontaneous contractile activity of the isolated rabbit jejunum. The addition of SNP (10(-5) to 10(-3) mol/l or ASN (10(-5) to 10(-3) mol/l) the organ bath inhibited the amplitude of the spontaneous contractions in rabbit isolated jejunum in a concentration dependent fashion, while L-NAME (3 x 10(-5) to 3 x 10 mol/l) was without effect. Methylene blue (3 x 10(-7) to 3 10(-6) mol/l), which inhibits soluble guanylate cyclase, and oxyhemoglobin (10(-5) mol/l), an NO scavenger, counteracted the effects of both SNP (3 x 10(-4) mol/l) and ASN (10(-4) mol/l). The spontaneous motility of rabbit jejunum was also inhibited in a concentration-dependent manner by 8-Br-cyclic GM (10(-5) to 10(-3) mol/l), a permeable analogue of cyclic GM. These results provide evidence that exogenous NO may inhibit spontaneous contractility and that this effect might be mediated, in part, by cyclic GMP, whereas endogenous NO does not seem to play a role in the regulation of the spontaneous motility of rabbit jejunum in vitro.
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PMID:Nitric oxide-donating compounds and cyclic GMP depress the spontaneous contractile activity of the isolated rabbit jejunum. 890 75

Pharmacological activation of muscarinic receptors located in the thoracic spinal cord evokes a marked increase in blood pressure and heart rate. We have previously demonstrated that the cardiovascular response to stimulation of spinal cord muscarinic cholinergic receptors is dependent upon a pharmacologically described ascending spino-bulbar pathway. The purpose of the study was to determine whether the blood pressure and heart rate responses to intrathecal (i.t.) injection of the muscarinic cholinergic receptor agonist carbachol are mediated by a local nitric oxide (NO)-generating system. Freely moving rats were previously prepared with chronic indwelling i.t. and intra-arterial catheters. Both the pressor and tachycardic responses produced by i.t. injection of carbachol were inhibited in a dose-dependent manner by i.t. pre-treatment with the NO synthase inhibitor N-omega-Nitro-L-arginine methylester (L-NAME). To confirm the site of action of the drugs employed in conscious rats, a separate group of rats was anesthetized, and using surgical procedures previously developed in this laboratory, drug distribution was limited specifically to the lower thoracic spinal cord. When carbachol was administered by i.t. injection and localized to the lower thoracic area, muscarinic cholinergic receptor stimulation again produced a marked pressor response, but without the accompanying tachycardia. The ability of N-omega-Nitro-L-arginine methylester (L-NAME) to inhibit the pressor response to carbachol in conscious rats was confirmed in anesthetized rats, although higher doses of L-NAME than those employed in conscious rats were required. L-NAME-induced inhibition of the carbachol-evoked pressor response was reversed by the L-, but not the D-isomer, of arginine. Moreover, i.t. pre-treatment with Methylene blue, that interferes with NO production and function, effectively inhibited the expression of the pressor response to i.t. injection of carbachol. The 'anti-muscarinic' action of L-NAME was not due to a direct interaction with spinal muscarinic receptors, as L-NAME did not significantly displace [3H]methyl-scopolamine from spinal cord membranes in vitro. The results of this study support the hypothesis that spinal muscarinic cholinergic receptors participate in a sympathoexcitatory pathway that interacts either directly or indirectly with a local NO-generating system involved in the regulation of blood pressure.
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PMID:Spinal muscarinic cholinergic and nitric oxide systems in cardiovascular regulation. 891 17

1. The aim of this study was to assess whether or not vasoactive nitric oxide (NO) stores exist within vascular tissue after lipopolysaccharide (LPS)-treatment. 2. Rat thoracic aortic rings (for contraction experiments) or whole thoracic aortae (for electron paramagnetic resonance (e.p.r.) spectroscopy) were incubated for 18 h at 37 degrees C in the absence (control) or in the presence of LPS (10 micrograms ml-1), with or without L-arginine (L-Arg, 1 mM), the substrate of NO synthase (NOS) or N omega-nitro-L-arginine methyl ester (L-NAME, 1 mM), an inhibitor of NOS. 3. Incubation of rat aortic rings with LPS and L-Arg resulted in a significant decrease of the maximum contractile response to noradrenaline (NA, 3 microM). Addition of L-NAME (3 mM) enhanced contraction towards control values. After precontraction with NA and L-NAME, addition of N-acetyl-L-cysteine (NAC, 0.1 to 10 mM) evoked a concentration-dependent relaxation in rings incubated with LPS and L-Arg, but not in control rings, rings incubated with LPS in the absence of L-Arg or rings incubated with LPS in the presence of L-Arg and L-NAME. Removal of the endothelium did not significantly modify the relaxation induced by NAC. Methylene blue (3 microM), an inhibitor of the activation of guanylyl cyclase by NO, completely abolished the relaxing effect of NAC. 4. The presence of protein-bound dinitrosyl non-haem iron complexes (DNIC) was detected by e.p.r. spectroscopy in aortae incubated with LPS and L-Arg, but not in control aortae. Furthermore in LPS-treated aortae, addition of NAC (20 mM) gave rise to the appearance of an e.p.r. signal characteristic of low molecular weight DNIC. 5. These results provide evidence that, within vascular tissue, NO generated from L-Arg by LPS-induced NOS activity can be stored as protein-bound DNIC in non-endothelial cells. Upon addition of NAC, low molecular weight DNIC are released from these storage sites and induce vascular relaxation probably through guanylyl cyclase activation.
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PMID:Evidence for N-acetylcysteine-sensitive nitric oxide storage as dinitrosyl-iron complexes in lipopolysaccharide-treated rat aorta. 893 35

Guanosine 3',5'-cyclic monophosphate (cGMP), a nitric oxide mediator, stimulates Na+/H+ exchange in brush-border vesicles of the renal cortex. The aim of the present work was to test whether the endothelium of the peritubular capillaries modulated the rate of proximal luminal acidification through the release of endothelium-derived nitric oxide (EDNO). Perfusion of the tubule lumen with dibutyryl cGMP increased net proton flux (J(H)). Two agents that elicit EDNO production, bradykinin (BK) and carbamylcholine (Cch), increased J(H) when added to the peritubular capillary perfusate. Bradykinin did not affect J(H) when the peritubular capillaries and the lumen were perfused with Na-free solution. Methylene blue (MB) and N(G)-nitro-L-arginine methyl ester (L-NAME) blocked the elevation in J(H) by Cch and also decreased basal J(H). Bradykinin increased cGMP content of isolated proximal convoluted tubules, but only if they were coincubated with endothelial cells. This effect of BK was blocked by L-NAME. The results suggest that the endothelium of the peritubular capillaries affects proximal tubule acidification through changes of cGMP in proximal tubule cells, probably via stimulation of Na+/H+ exchanger.
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PMID:Control of proximal tubule acidification by the endothelium of the peritubular capillaries. 912 96

This study has evaluated the possible role played by the L-arginine-nitric oxide pathway in the vasorelaxant action of the hydroalcoholic extract from Eugenia uniflora, and fractions from the extract, in rings of rat thoracic aorta. The addition of an increasing cumulative concentration of hydroalcoholic extract from E. uniflora (1-300 micrograms mL-1) caused a concentration-dependent relaxation response in intact endothelium-thoracic aorta rings pre-contracted with noradrenaline (30-100 nM). The IC50 value, with its respective confidence limit, and the maximum relaxation (Rmax) were 7.02 (4.77-10.00) micrograms mL-1 and 83.94 +/- 3.04%, respectively. The removal of the endothelium completely abolished these responses. The nitric oxide synthase inhibitors N omega-nitro-L-arginine (L-NOARG, 30 microM) and N omega-nitro-L-arginine methyl ester (L-NAME, 30 microM), inhibited the relaxation (Rmax) to -10.43 +/- 7.81% and -3.69 +/- 2.62%, respectively. In addition, L-arginine (1 mM), but not D-arginine (1 mM), completely reversed inhibition by L-NOARG. Methylene blue (30 microM), a soluble guanylate cyclase inhibitor, reduced the relaxation induced by the extract to 14.60 +/- 7.40%. These data indicate that in the rat thoracic aorta the hydroalcoholic extract, and its fractions, from the leaves of E. uniflora have graded and endothelium-dependent vasorelaxant effects.
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PMID:Analysis of the role of nitric oxide in the relaxant effect of the crude extract and fractions from Eugenia uniflora in the rat thoracic aorta. 923 44

In pentobarbital-anesthetized rats the intrathecal (i.t.) injection of the nitric oxide (NO) precursor, L-arginine (10 and 20 micromol), elicited a decrease in the mean blood pressure (MBP) whereas the inhibitor of the NO synthase (NOS) N(G)-nitro-L-arginine methyl ester (L-NAME; 0.1-10 micromol) produced a dose-dependent pressor effect. The pressor response to L-NAME was prevented by pretreatment with L-arginine. Neither D-arginine nor D-NAME modified the MBP. The NO donor sodium nitroprusside (SNP; 0.125 and 0.25 micromol, i.t.) induced a hypotensive response followed by a pressor effect. The dual response to SNP as well as the hypotensive effect of L-arginine were abolished by the guanylate cyclase inhibitor Methylene blue (0.3 micromol, i.t.). Nicotinic ganglionic blockade by hexamethonium (10 mg/kg, i.v.) reduced the hypotensive effects of both L-arginine and SNP and prevented almost completely the pressor effects of either L-NAME or SNP. The pressor effect of L-NAME was abolished by 2-amino-5-phosphonovaleric acid (APV; 30 nmol, i.t.), a selective antagonist of glutamate receptors of the NMDA subtype. These results suggest that in the spinal cord of pentobarbital-anesthetized rats NO exerts both inhibitory and excitatory effects on the preganglionic sympathetic nerve activity related to the control of the BP. The synthesis of NO appears to be tonically activated through the stimulation of spinal glutamate receptors of the NMDA subtype.
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PMID:Possible participation of spinal nitric oxide in the control of the blood pressure in anesthetized rats. 929 94

Capsaicin (5 x 10[-8] to 5 x 10[-5] M) produced a non-adrenergic and non-cholinergic phasic relaxation in a concentration-dependent manner in isolated dog urethral preparations precontracted by noradrenaline. The mode of action of capsaicin was investigated with special reference to the possible involvement of endogenous nitric oxide (NO). A marked tachyphylaxis was observed in the responses to capsaicin. Pretreatment with NG-nitro-L-arginine-methyl-ester (L-NAME) prevented or markedly reduced the inhibitory effect of L-NAME. Methylene blue inhibited the capsaicin-induced relaxation. In preparations stored at 4 degrees C for 72 h, the reduction in the capsaicin-induced relaxation was significantly greater than that in the relaxation induced by either electrical field stimulation or by sodium nitroprusside. We conclude that capsaicin produces an endogenous-NO-dependent relaxation in the isolated dog urethra via mechanisms that deteriorate during cold storage of the preparations.
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PMID:Capsaicin-induced nitric-oxide-dependent relaxation in isolated dog urethra. 936 76

Prior studies have demonstrated that the erectile response in the rat penis is androgen dependent and is mediated by nitric oxide (NO), the neurotransmitter synthesized by the enzyme nitric oxide synthase (NOS). The present studies used L-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NOS, to determine if androgens also regulate alternative pathways leading to the erectile response but not mediated by NO. Castrated rats that were treated with L-NAME (L-NAME CASTRATE) exhibited little or no increase in intracavernosal pressure in response to stimulation of the major pelvic ganglion. This ganglion controls blood flow into the penis and, when stimulated, normally leads to erection. However, when castrated animals were treated with testosterone along with L-NAME (L-NAME TESTO), the animals responded to the ganglionic stimulation with increased intracavernosal pressure. This finding suggests that there are other androgen-dependent pathways that lead to penile erection but are not mediated by NO. Erection occurred in both L-NAME CASTRATE and L-NAME TESTO rats in response to intracavernosal injection of sodium nitroprusside (an NO donor drug), proving that the NO responsive mechanisms were unaffected by the inhibition of NOS activity. To investigate further the nature of this NO independent pathway, L-NAME CASTRATE and L-NAME TESTO rats were treated with either zaprinast (a specific phosphodiesterase 5 inhibitor), which would block the breakdown of cGMP to 5'GMP, or methylene blue (an inhibitor of guanylate cyclase) to prevent the synthesis of cGMP. Zaprinast treatment led to increased erectile response in L-NAME TESTO rats but not in L-NAME CASTRATE rats, demonstrating that androgen-sensitive alternative pathways increased guanylate cyclase activity. Methylene blue inhibited the erectile response in all treatment groups, showing that cyclic GMP is critical to the NO-independent pathway as well as the NO-dependent pathway. Taken together, these results support the hypothesis that androgens maintain the erectile response by alternate pathways, including one that is independent of NO but involves the synthesis of cyclic GMP.
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PMID:Androgenic maintenance of the rat erectile response via a non-nitric-oxide-dependent pathway. 943 31

1. The effect of Tityus serrulatus scorpion venom and its toxin components on the rabbit isolated corpus cavernosum was investigated by use of a bioassay cascade. 2. Tityus serrulatus venom (3-100 microg), acetylcholine (ACh; 0.3-30 nmol) and glyceryl trinitrate (GTN; 0.5-10 nmol) dose-dependently relaxed rabbit isolated corpus cavernosum preparations precontracted with noradrenaline (3 microM). The selective soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3,-alquinoxalin-1-one] (ODQ; 30 microM) increased the basal tone of the rabbit isolated corpus cavernosum and abolished the relaxations induced by the agents mentioned above. Methylene blue (30 microM) also inhibited the relaxations induced by Tityus serrulatus venom but, in contrast to ODQ, the inhibition was irreversible. 3. The non-selective NO synthase (NOS) inhibitors Nomega-nitro-L-arginine methyl ester (L-NAME; 10 microM) and NG-iminoethyl-L-ornithine (L-NIO; 30 microM) also increased the tone of the rabbit isolated corpus cavernosum and markedly reduced both ACh- and Tityus serrulatus venom-induced relaxations without affecting those evoked by GTN. The inhibitory effect was reversed by infusion of L-arginine (300 microM), but not D-arginine (300 microM). The neuronal NOS inhibitor 1-(2-trifluoromethylphenyl) imidazole (TRIM, 100 microM) did not affect either the tone of the rabbit isolated corpus cavernosum or the relaxations induced by ACh, bradykinin (Bk), Tityus serrulatus venom and GTN. TRIM was approximately 1,000 times less potent than L-NAME in inhibiting rabbit cerebellar NOS in vitro, as measured by the conversion of [3H]-L-arginine to [3H]-L-citrulline. 4. The protease inhibitor aprotinin (Trasylol; 10 microg ml[-1]) and the bradykinin B2 receptor antagonist Hoe 140 (D-Arg-[Hyp3,Thi5,D-Tic7, Oic8]-BK; 50 nM) did not affect the rabbit isolated corpus cavernosum relaxations induced by Tityus serrulatus venom. The ATP-dependent K+ channel antagonist glibenclamide (10 microm) and the Ca2+-activated K+ channel antagonists apamin (0.1 microM) and charybdotoxin (0.1 microM) also failed to affect the venom-induced relaxations. Similarly, the K+ channel blocker tetraethylammonium (TEA; 10 microM) had no effect on the venom-induced relaxations. 5. Capsaicin (3 and 10 nmol) relaxed the rabbit isolated corpus cavernosum in a dose-dependent and non-tachyphylactic manner. Ruthenium red (30 microM), an inhibitor of capsaicin-induced responses, markedly reduced the relaxations caused by capsaicin, but failed to affect those induced by Tityus serrulatus venom. L-NAME (10 microM) had no effect on the capsaicin-induced relaxations of the rabbit isolated corpus cavernosum. 6. The sodium channel blocker tetrodotoxin (TTX; 1 microM) abolished the relaxations of the rabbit isolated corpus cavernosum induced by Tityus serrulatus venom without affecting those evoked by capsaicin, ACh and GTN. Tetrodotoxin (1 microM) also promptly reversed the response to the venom when infused during the relaxation phase. 7. The bioassay cascade of the toxin components purified from Tityus serrulatus venom revealed that only fractions X, XI and XII caused dose-dependent relaxations of the rabbit isolated corpus cavernosum and these were markedly reduced by either TTX (1 microM) or L-NAME (10 microM). 8. Our results indicate that Tityus serrulatus scorpion venom (and the active fractions X, XI and XII) relaxes rabbit corpus cavernosum via the release of NO. This release is specifically triggered by the activation of capsaicin-insensitive cavernosal non-adrenergic non-cholinergic (NANC) fibres, that may possibly be nitrergic neurones. Tityus serrulatus venom may therefore provide an important tool for understanding further the mechanism of NANC nitrergic nerve activation.
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PMID:Effect of Tityus serrulatus scorpion venom on the rabbit isolated corpus cavernosum and the involvement of NANC nitrergic nerve fibres. 950 84

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