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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Strips of muscle from sheep bladder neck were set up for tension recording and subjected to electrical field stimulation (EFS) to stimulate their intramural nerves. 2. In the presence of atropine (1 microM) and guanethidine (1 microM), the response to 1 Hz EFS was biphasic, characterized by a relaxation during the stimulus period, followed by a post-stimulus contraction. A similar biphasic response was also seen following bolus application of nitric oxide (NO). 3. In the absence of atropine and guanethidine, the relaxations were masked by contractions during stimulation; however, the post-stimulus contraction were unaffected. L-NAME (100 microM) blocked the post-stimulus contractions and L-arginine (1 mM) restored them, suggesting that they were NO-mediated. 4. M&B 22948, a phosphodiesterase inhibitor, prolonged the relaxations and abolished the post-stimulus contractions. This suggests that rapid removal of cyclic GMP is required for post-stimulus contraction to occur. 5. When the number of pulses in the stimulus train was kept constant, the size of the post-stimulus contraction increased as the duration of the preceding period of stimulation increased. Maximal post-stimulus contractions were obtained following stimulation for > 40 s. 6. The L-channel antagonist, nifedipine (1 microM) and verapamil (1 microM), had little effect on the amplitude of the post-stimulus contractions. 7. In contrast, ryanodine-(8 microM) reduced the post-stimulus contractions by over 90%. Caffeine (20 mM) also abolished the post-stimulus contractions and cyclopiazonic acid (CPA, 10 microM) reduced them by 76%. However, in the presence of CPA a slower post-stimulus contraction developed. Nifedipine (1 microM) reduced this by 40%. 8. In conclusion, these results support a role for NO in the post-stimulus contraction of the sheep bladder neck muscle. The post-stimulus contraction depends more on release of intracellular Ca2+, than Ca2+ influx through L-type channels.
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PMID:Characteristics of the NANC post-stimulus ('rebound') contraction of the urinary bladder neck muscle in sheep. 858 Dec 84

1. The receptors mediating the vasodilator responses to adenosine in the isolated mesenteric arterial bed of the rat were identified by use of selective agonists and antagonists and the involvement of the endothelium was examined. 2. Adenosine-mediated dilatation of the mesentery was potentiated by the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM), but in contrast, removal of the endothelium substantially reduced the responses to adenosine. 3. The order of potency of adenosine receptor agonists was: 5'-N-ethylcarboxamidoadenosine (NECA) > 2-p-(-2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) > 2-chloro-N6-cyclopentyl-adenosine (CCPA) > or = adenosine, suggesting the presence of A2A receptors. 4. Adenosine-mediated dilatation was inhibited by the non-selective adenosine receptor antagonist, 8-phenyltheophylline (3 microM) and by the A2A receptor antagonist 8-(3-chlorostyryl)caffeine (500 nM), but was unaffected by the A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 10 nM). 5. Reducing the pH of the perfusate to 6.8 potentiated the actions of both CGS 21680 and adenosine, but the vasodilator effects of carbachol were the same at both pH values. The adenosine response at the lower pH as at pH 7.4, was unaffected by DPCPX. The actions of the nitrovasodilator, sodium nitroprusside, were also potentiated at pH 6.8 relative to those at the higher pH value but smaller responses were obtained at the lower pH value with forskolin, a stimulator of adenylyl cyclase, than at pH 7.4. 6. It is concluded that the adenosine receptor mediating dilatation of the rat mesenteric arterial bed is of the A2A subtype, that the response, under the conditions used, is apparently partly dependent on the endothelium (but not due to the release of nitric oxide), and that the response to activation of this receptor is potentiated by a reduction in pH which is similar to that seen in ischaemic conditions.
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PMID:Effects of pH on responses to adenosine, CGS 21680, carbachol and nitroprusside in the isolated perfused superior mesenteric arterial bed of the rat. 859 Sep 83

The effects of caffeine and nitric oxide synthesis inhibition on the antinociceptive action of ketorolac were assessed using the pain-induced functional impairment model in the rat. Nociception was induced by the intra-articular injection of uric acid. Ketorolac, but not caffeine, produced an antinociceptive effect which was reduced by NG nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthesis. Caffeine coadministration potentiated the ketorolac effect. L-NAME induced a dose-dependent reduction of this potentiation. The results suggest the participation of the L-arginine-nitric oxide-cyclic GMP pathway in the caffeine potentiation of ketorolac-induced antinociception.
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PMID:Effect of caffeine coadministration and of nitric oxide synthesis inhibition on the antinociceptive action of ketorolac. 885 98

Adult rats treated IP with domoic acid at 0, 0.22, 0.65, or 1.32 mg/kg were tested for passive avoidance (PA), auditory startle (AS), or conditioned avoidance (CAR) behaviors. Clinical signs were observed only at the 1.32 mg/kg dose level. Within 24 h of dosing, rats surviving a dose of 1.32 mg/kg exhibited transient decreased body weight and exaggerated AS responding. Startle latency and habituation, PA, and CAR were not affected. Examination of brains from six rats per group revealed a subset (2/6) of animals receiving 1.32 mg/kg domoic acid with degenerating neurons in the hippocampal CA1/CA3 subregions and gliosis. The decreased body weight and increased startle suggest a hyperreactivity syndrome possibly related to neuronal degeneration in the hippocampus. In a separate experiment, domoic acid at an IP dose of 0.93 mg/kg was found to produce hypomotility in addition to a decrease in body weight. Both effects were reduced by pretreatment with scopolamine (2 mg/kg), but not with caffeine (30 mg/kg), indicating a possible cholinergic involvement in domoate's toxicity.
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PMID:Domoic acid: neurobehavioral and neurohistological effects of low-dose exposure in adult rats. 894 43

The present study investigated the effects of nitric oxide synthase (NOS) inhibitors on the seizure threshold of DMCM in mice. The seizure threshold of DMCM was evaluated using an intravenous infusion technique. The threshold of DMCM was significantly decreased by pretreatment with N-nitro-L-arginine (NOARG; 8 mg/kg) and N-nitro-L-arginine methyl ester (L-NAME; 100 mg/kg), but not with D-NAME. Furthermore, these NOS inhibitors also decreased the threshold for pentylenetetrazole-induced seizure. However, the threshold for caffeine-induced seizure was not affected by NOARG. These results suggest that the endogenous NO system may play an important role in the expression of seizure by GABA(A) receptor inhibitory agents (DMCM and PTZ).
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PMID:Aggravation of DMCM-induced seizure by nitric oxide synthase inhibitors in mice. 918 Mar 70

The roles of nitric oxide, adenosine and cortical arousal in the response to 7.5% CO2 inhalation were investigated by measuring cerebral blood flow bilaterally in the rat somatosensory cortices with laser-Doppler flow probes. Administration of N(omega)-nitro-L-arginine methyl ester (L-NAME; 20 mg/kg, i.v.) significantly attenuated the response to hypercapnia (mean decrease of 47%). This effect was partially reversed by a subsequent administration of L-arginine. Caffeine (10 mg/kg, i.v.) also significantly reduced hypercapnic responses (mean decrease of 44%). Caffeine administration was also associated with a tendency for animals to exhibit electrocorticographic signs of arousal; often associated with a reduction in the attenuation of the flow response to CO2 inhalation. 8-(3-Chlorostyryl) caffeine (CSC, 1.0 mg/kg), a selective antagonist at adenosine A2a striatal receptors failed to attenuate CO2-evoked responses, whereas CGS 15943, a less selective A2a receptor antagonist, significantly reduced CO2 responses. These data from the rat suggest (1) that both nitric oxide and adenosine may contribute to pial arteriolar vasodilatation during hypercapnia, and (2) that CO2 inhalation acts as a potent stimulus for cortical arousal, with enhanced neuronal activity contributing to the vascular response. The effects of administration of adenosine antagonists, such as the methylxanthines antagonists caffeine and theophylline, on CBF responses to hypercapnia can potentially be negated by the ability of these agents to facilitate CO2-induced cortical arousal.
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PMID:Hypercapnia-induced increases in cerebral blood flow: roles of adenosine, nitric oxide and cortical arousal. 920 26

The aim of the present study was to investigate the effect of nitric oxide (NO) on the relaxant activity of caffeine and aminophylline on rat myometrial strips. Uteri of pregnant Wistar rats were removed and suspended in 10-ml organ baths containing 37 degreesC Krebs bicarbonate solution gassed with 95% O2 and 5% CO2. The significance of the results was assessed by Student's t-test and P<0.05 was considered significant. A relaxant effect was observed with 10(-5)-10(-2) M caffeine (n=8) and aminophylline (n=6) on pregnant rat myometrial strips precontracted with 64 mM K+ (IC50=4.21+/-0.35 and 4.25+/-0.26, respectively). Incubation with 10(-5) M methylene blue, 10(-5) M haemoglobin, 10(-6) M Nomega-nitro-L-arginine methyl ester (L-NAME), 2x10(-7) M forskolin and 10(-6) M zaprinast exerted no effect on the relaxations (P>0.05). When the concentration of external Ca2+ was decreased to 0.5 mM or increased to 4.5 mM from the control level of 1.5 mM, the concentration-inhibition curves for caffeine and aminophylline shifted to the left or to the right, respectively. Our results suggest that: (1) the L-arginine-NO-cGMP system has no effect on the inhibition induced by caffeine and aminophylline on K+ induced contractions of pregnant rat myometrium; (2) this inhibitory effect is not mediated by cAMP; (3) cGMP does not play a role on the relaxant effect of these drugs; and (4) that Ca2+ plays the major role on the relaxations obtained with methylxanthine derivatives on pregnant rat uterus. (c) 1998 The Italian Pharmacological Society.
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PMID:The probable role of nitric oxide on the relaxations obtained by caffeine and aminophylline in rat uterus. 980 19

The endothelium-dependent and -independent relaxant effect of procaine was examined in isolated rat aortic rings. Procaine induced relaxation of arteries precontracted with phenylephrine or with 60 mM K+ in a concentration-dependent manner (0.01-3 mM). Procaine (1 mM) inhibited the transient contraction induced by caffeine (10 mM) in Ca2+-free Krebs solution. Removal of the endothelium caused a rightward shift of the concentration-response curve for procaine. N(G)-Nitro-L-arginine (L-NNA, 10-100 microM), N(G)-nitro-L-arginine methyl ester (L-NAME, 100 microM) and methylene blue (1-10 microM) significantly attenuated the procaine-induced relaxation without affecting the maximal response. L-Arginine (1 mM) partially but significantly antagonized the effect of L-NAME (100 microM). Pretreatment of endothelium-intact aortic rings with procaine (1 mM) or with acetylcholine (10 microM) significantly elevated the tissue contents of cyclic GMP and this increase was inhibited in the presence of 100 microM L-NNA. Tetrapentylammonium ions (1-3 microM) reduced the procaine-induced relaxation in both endothelium-intact and -denuded arteries. Tetrapentylammonium ions (3 microM) did not affect the procaine-induced relaxation of 60 mM K+-contracted arteries. Tetraethylammonium ions (3 mM) inhibited the procaine-induced relaxation. In contrast, iberiotoxin (100 nM), glibenclamide (3 microM), 4-aminopyridine (3 mM) and indomethacin (10 microM) had no effect. These results indicate that the procaine-induced relaxation may be mediated through multiple mechanisms. A substantial portion of the procaine-induced relaxation in rat aorta was caused by nitric oxide but not by other endothelium-derived factors. The activation of tetrapentylammonium- and tetraethylammonium-sensitive K+ channels contributes in part to the procaine-induced vasorelaxation. Besides, procaine may directly inhibit both external Ca2+ entry and internal Ca2+ release in aortic smooth muscle cells.
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PMID:Contribution of nitric oxide and K+ channel activation to vasorelaxation of isolated rat aorta induced by procaine. 1007 97

1. Mechanisms underlying spontaneous rhythmical contractions have been studied in irideal arterioles of the rat using video microscopy and electrophysiology. 2. Rhythmical contractions (4 min-1) were more common during the second and third postnatal weeks and were always preceded by large, slow depolarizations (5-40 mV). 3. Spontaneous contractions were unaffected by tetrodotoxin (1 microM), neurotransmitter receptor antagonists, the sympathetic neurone blocker, guanethidine (5 microM) or sensory neurotoxin, capsaicin (1 microM). 4. Stimulation of sensory nerves inhibited spontaneous activity and this was not prevented by L-NAME (10 microm). 5. L-NAME (10 microm) caused an increase in frequency of spontaneous contractions, while forskolin (30 nM), in the presence of L-NAME, abolished spontaneous, but not nerve-mediated, contractions. 6. Spontaneous activity was not affected by felodipine (1 nM) or nifedipine (1 microM), but was abolished by cadmium chloride (1 microM) or superfusion with calcium-free solution. 7. Caffeine (1 mM), thapsigargin (2 microM) and cyclopiazonic acid (3 microM), but not ryanodine (3 microM), abolished spontaneous and nerve-mediated contractions. After preincubation in L-NAME (10 microM), cyclopiazonic acid abolished spontaneous contractions only. 8. Spontaneous depolarizations and contractions were abolished by 18alpha-glycyrrhetinic acid (20 microM). 9. Results suggest that spontaneous rhythmical contractions are myogenic and result from the cyclical release of calcium from intracellular stores, without a contribution from voltage-dependent calcium channels. Intercellular coupling through gap junctions appears to be essential for co-ordination of these events which could be modulated by nitric oxide and increases in cAMP. The possibility that different intracellular stores underly spontaneous and nerve-mediated contractions is discussed.
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PMID:Mechanisms underlying spontaneous rhythmical contractions in irideal arterioles of the rat. 1058 19

The present study was intended to examine the relaxant effects of berberine in rat isolated mesenteric arteries. Berberine produced a rightward shift of the concentration-response curve to phenylephrine and significantly reduced the maximal contractile response to phenylephrine. Berberine (10(-7)-3x10(-5) M) also relaxed the phenylephrine- and 9,11-dideoxy-11alpha, 9alpha-epoxy-methanoprostaglandin F(2alpha)-precontracted arteries with respective IC(50) values of 1.48+/-0.16x10(-6) and 2.23+/-0. 22x10(-6) M. Removal of a functional endothelium significantly attenuated the berberine-induced relaxation (IC(50): 4.73+/-0. 32x10(-6) M) without affecting the maximum relaxant response. Pretreatment with N(G)-nitro-L-arginine methyl ester (L-NAME) or methylene blue reduced the relaxant effect of berberine, and L-arginine (10(-3) M) partially antagonized the effect of L-NAME. In contrast, pretreatment with 10(-6) M glibenclamide or 10(-5) M indomethacin had no effect. Berberine (10(-5) M) reduced over by 50% the transient contraction induced by caffeine or phenylephrine in endothelium-denuded rings bathed in Ca(2+)-free Krebs solution. Pretreatment with putative K(+) channel blockers, such as tetrapentylammonium ions (1-3x10(-6) M), 4-aminopyridine (10(-3) M), or Ba(2+) (3x10(-4) M), significantly attenuated the berberine-induced relaxation in endothelium-denuded arteries. In contrast, tetraethylammonium ions (3x10(-3) M), charybdotoxin (10(-7) M) or glibenclamide (10(-6) M) were without effect. Berberine reduced the high-K(+)-induced sustained contraction and the relaxant response to berberine was greater in rings with endothelium (IC(50): 4.41+/-0.47x10(-6) M) than in those without endothelium (IC(50): 8.73+/-0.74x10(-6) M). However, berberine (10(-6)-10(-4) M) did not affect the high-K(+)-induced increase of intracellular [Ca(2+)] in cultured aortic smooth muscle cells. Berberine did not affect active phorbol ester-induced contraction in Ca(2+)-free Krebs solution. In addition, berberine inhibited proliferation of cultured rat aortic smooth muscle cells with an IC(50) of 2.3+/-0.43x10(-5) M. These findings suggest that berberine could act at both endothelium and the underlying vascular smooth muscle to induce relaxation. Nitric oxide from endothelium may account primarily for the berberine-induced endothelium-dependent relaxation, while activation of tetrapentylammonium-, 4-aminopyridine- and Ba(2+)-sensitive K(+) channels, inhibition of intracellular Ca(2+) release from caffeine-sensitive pools, or a direct relaxant effect, is likely responsible for the berberine-induced endothelium-independent relaxation. Mechanisms related to either Ca(2+) influx or protein kinase C activation may not be involved. Both vasorelaxant and antiproliferative effects may contribute to a long-term benefit of berberine in the vascular system.
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PMID:Vasorelaxant and antiproliferative effects of berberine. 1088 19


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