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)

Small arteries (internal diameter 376 +/- 69 microns) from the proximal intestine region of the rainbow trout were mounted in a myograph apparatus where changes in isometric tension could be recorded. VIP (vasoactive intestinal polypeptide) caused a concentration-dependent relaxation (10(-9)-3 x 10(-7) M) of vessels precontracted with the alpha-adrenoceptor agonist phenylephrine (10(-5) M). The nitric oxide synthase inhibitor L-NAME (10(-4) M) did not affect the VIP-relaxation, neither did the lipoxygenase inhibitor esculetin (10(-5) M). However, the cyclooxygenase inhibitor indomethacin (10(-6) M) shifted the concentration-response curve significantly to the right. The VIP-relaxation was still present after mechanical removal of the endothelium. Sodium nitroprusside (10(-9)-10(-6) M) caused a concentration-dependent relaxation of the precontracted vessel, indicating the presence of soluble guanylate cyclase in the vascular smooth muscle cells. VIP-immunoreactivity was found in varicose nerve fibers in these vessels, but nitric oxide synthase-immunoreactivity could not be demonstrated. These results suggest that in rainbow trout, as in mammals, VIP is an endogenous vasodilating neuropeptide. No endothelium-dependent mechanism seems to be involved, neither is production of nitric oxide. Instead the relaxation is mediated, at least in part, via prostaglandin synthesis.
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PMID:Vip-induced relaxation of small arteries of the rainbow trout, Oncorhynchus mykiss, involves prostaglandin synthesis but not nitric oxide. 908 41

1. This article examines the effects of hypoxia on the contractile response of isolated human umbilical artery strips to 5-hydroxytryptamine (5-HT). 2. Hypoxic conditions produce a large increase in the contractile response to 5-HT without a significant alteration of the sensitivity evaluated at the level of the pD2 value. Indomethacin (10 microM) reduced hypoxia-induced potentiation of the response to 5-HT and decreased the response to the monoamine under oxygenated conditions. 1-NAME (100 microM) did not further increase the effect of hypoxia on the vessel response to 5-HT and increased the response to 5-HT under oxygenated conditions. 3. Taken together, these results suggest that, at least partially, the response of human umbilical artery strips to 5-HT depends on 5-HT release of a contracting prostanoid which is a product of the cyclooxygenase pathway. Furthermore, during hypoxia in human umbilical artery strips, there appears to be impairment of the basal production and/or release of EDRF/NO. 4. A subthreshold concentration of prostaglandin F2 alpha (1 nM) potentiates the response to 5-HT in indomethacin-pretreated umbilical artery strips. The data raise the possibility that prostaglandin F2 alpha might be the prostanoid released during hypoxia, which in turn potentiates the response of the human umbilical artery to 5-HT.
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PMID:Hypoxia and response of human umbilical artery strips to 5-hydroxytryptamine: role of prostaglandin F2 alpha. 911 81

Recent evidence suggests that newer vasoselective dihydropyridine calcium antagonists are not cardiodepressant and may be useful in the treatment of heart failure. No data are available on the efficacy of clentiazem, a vasoselective benzothiazepine-like calcium antagonist, in this pathological condition. Therefore, our objective was to assess coronary and cardiac sensitivity to clentiazem in an experimental model of chronic heart failure (cardiomyopathic hamster, UM-X7.1, > 200 day old). Left ventricular developed pressure (LVP) and coronary flow changes were assessed in isolated, perfused failing hearts and in normal Syrian hamster hearts. Clentiazem dose-response curves for both coronary dilation and negative inotropic effects were determined under control conditions and in the presence of the nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine (L-NAME, 30 microM), and the cyclooxygenase inhibitor, indomethacin (10 microM). Baseline hemodynamics indicate a significant reduction in both LVP and coronary perfusion in failing hearts. Cardiac sensitivity to the negative inotropic effects of clentiazem were similar in normal and failing hearts (IC50 = 677 nM and 734 nM, respectively). However, the clentiazem-induced increase in coronary flow was significantly attenuated in failing hearts (EC50 = 56 +/- 9 nM vs. 15 +/- 3 nM in normal hearts, p < 0.01). To better characterize the reduced coronary sensitivity to clentiazem in the presence of heart failure, the contributions of the NO synthase and the cyclooxygenase pathways were evaluated. Although coronary sensitivity to clentiazem was significantly reduced in the presence of L-NAME, this attenuation was of the same magnitude in normal and failing hearts, suggesting that coronary "desensitization" to clentiazem in failing hearts does not involve the NO synthase pathway. Experiments carried in the presence of indomethacin indicate that the reduced coronary sensitivity to clentiazem observed in failing hearts does not involve the cyclooxygenase pathway. In conclusion, reduced coronary sensitivity to the vasoselective calcium antagonist clentiazem was observed in the failing hamster heart, while no exacerbation of clentiazem's cardiodepressant actions was present. Although the mechanisms involved in the vascular desensitization to clentiazem are still unknown, our findings may provide an additional explanation for the variable efficacy of calcium antagonists in the treatment of heart failure.
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PMID:Coronary and cardiac sensitivity to the vasoselective benzothiazepine-like calcium antagonist, clentiazem, in experimental heart failure. 914 Jun 81

The leukotriene synthesis inhibitor (LSI) BAY X 1005 was tested in the arachidonic acid (AA)-induced mouse ear inflammation test (AA-MEIT) alone and in combination with other representative anti-inflammatory compounds for antiedematous effects. When BAY X 1005 was used as a monotherapy, the ED50 (half-maximal effect) was observed at 5.1 mg/kg per os (p.o.) and at 0.8 microg for topical application. The maximal inhibition of edema formation was estimated to be 63% for p.o. application and 54% for topical application. Furthermore, experiments were carried out in which the animals were conditioned with a combination of the H1/5-HT receptor antagonists pyrilamine and methysergide in addition to treatment with BAY X 1005. This conditioning treatment alone, without BAY X 1005, resulted in a 45 +/- 13% reduction in edema formation. ED50 substance effects were observed at 5.3 mg/kg p.o. and at 0.02 microg per ear for topical application. The maximal inhibition of edema formation in the conditioned groups was 82% for the oral administration of BAY X 1005 and 72% for the topical application. To further characterize the antiinflammatory properties of BAY X 1005 in the conditioned and unconditioned AA-MEIT, BAY X 1005 was tested in combination with the nitric oxide (NO) synthase inhibitor L-NAME, with the cyclooxygenase inhibitor indomethacin, and in combination with both compounds. BAY X 1005 consistently exerted anti-inflammatory effects in the AA-MEIT. The effects of a combination of different inhibitors of inflammatory mediators were not simply additive in this model, as was demonstrated in the case of the combination of L-NAME and indomethacin where a smaller inhibition than with either substance alone was observed. In the conditioned model, a combination of BAY X 1005 with L-NAME or indomethacin, or with both compounds together was less effective than the monotherapy with BAY X 1005. Taken together, these data suggest that cyclooxygenase products and NO have little effect on edema formation in the conditioned and unconditioned AA-MEIT model and that their interaction with leukotrienes is of minor quantitative importance. Our results underline the complexity of the AA-MEIT model and provide a rationale for H1/5-HT-conditioning animals to compensate for peculiarities in the mouse-specific mediator spectrum and to recognize the importance of the leukotriene-specific inflammatory response.
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PMID:Antiedematous effects of combination therapies with the leukotriene synthesis inhibitor BAY X 1005 in the archidonic acid-induced mouse ear inflammation test. 915 Mar 76

The contractile effect of norepinephrine (NE) on isolated rabbit bronchial artery rings (150-300 microns in diameter) and the role of alpha 1- and alpha 2-adrenoceptors (AR) on smooth muscle and endothelium were studied. In intact arteries, NE increased tension in a dose-dependent manner, and the sensitivity for NE was further increased in the absence of endothelium. In intact but not in endothelium-denuded arteries, the response to NE was increased in the presence of both indomethacin (Indo; cyclooxygenase inhibitor) and NG-nitro-L-arginine methyl ester [L-NAME; nitric oxide (NO) synthase inhibitor], indicating that two endothelium-derived factors, NO and a prostanoid, modulate the NE-induced contraction. The alpha 1-AR antagonist prazosin shifted the NE dose-response curve to the right, and phenylephrine (alpha 1-AR agonist) induced a dose-dependent contraction that was potentiated by L-NAME or removal of the endothelium. The sensitivity to NE was increased slightly by the alpha 2-AR antagonists yohimbine and idazoxan, and this effect was abolished by Indo or removal of the endothelium. Similarly, contractions induced by UK-14304 (alpha 2-AR agonist) were potentiated by Indo or removal of the endothelium. These results suggest that NE-induced contraction is mediated through activation of alpha 1- and alpha 2-ARs on both smooth muscle and endothelium. Activation of the alpha 1- and alpha 2-ARs on the smooth muscle causes contraction, whereas activation of the endothelial alpha 1- and alpha 2-ARs induces relaxation through release of NO (alpha 1-ARs) and a prostanoid (alpha 2-ARs).
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PMID:Norepinephrine-induced contraction of isolated rabbit bronchial artery: role of alpha 1- and alpha 2-adrenoceptor activation. 917 59

We have previously reported that there is an altered response to mast cell-mediated inflammation in copper-deficient rats. In the current study we determined the microvascular reactivity to inflammatory stimuli with lipopolysacccharide (LPS) during dietary copper restriction. Male Sprague-Dawley rats were fed purified diets which were either copper-adequate (CuA, 6 micrograms Cu/g) or copper-deficient (CuD, 0.4 micrograms Cu/g) for 4 weeks. Rats were anesthetized and the cremaster muscle was prepared for in vivo television microscopy. Arteriolar diameters were measured and then 2.5 mg/kg LPS was injected i.p. In separate groups, animals were pretreated with the NO-synthase inhibitor L-NAME (2 x 10(-4) M), the cyclooxygenase inhibitor ibuprofen (9.6 x 10(-5) M) or the histamine receptor antagonist diphenhydramine (DPH, 10(-6) M). LPS caused arteriolar dilation in both dietary groups with the response being significantly greater in the CuD group. Ibuprofen and DPH but not L-NAME, each significantly reduced but did not block the dilation in the CuD group. Ibuprofen and DPH together blocked the dilation. These results suggest that dietary copper deficiency increases arteriolar dilation to LPS. The mechanism appears to involve a greater response to arachidonic acid metabolites and histamine but not NO.
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PMID:Arteriolar dilation to endotoxin is increased in copper-deficient rats. 917 21

The effect of NG-monomethyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine methyl ester (L-NAME) on acetylcholine (ACh) induced relaxation of rat intrapulmonary artery and celiac artery ring segments was studied in vitro with and without meclofenamate pretreatment. L-NMMA, and to a lesser extent L-NAME, raised baseline tone more in pulmonary than celiac arteries. Pretreatment of pulmonary and celiac artery rings with meclofenamate did not alter this contractile effect. Pulmonary artery and celiac artery ring segments were precontracted with phenylephrine, and cumulative concentration-relaxation curves to ACh were obtained before and after incubation of the rings with L-NAME or L-NMMA. L-NAME inhibited the ACh-induced relaxation of pulmonary arterial rings at 10000 fold lower concentrations than those needed to only partly inhibit the ACh-induced relaxation of celiac artery rings. L-NMMA (10-300 microM) inhibited the ACh-induced relaxation of pulmonary arterial rings in a concentration-dependent manner, whereas L-NMMA (300 microM) only partially inhibited the ACh-induced relaxation of celiac artery rings. The inhibition of ACh-induced relaxation by L-NAME and to a lesser extent by L-NMMA was more when pulmonary and celiac artery rings were pretreated with meclofenamate (1.0 microM). These results suggest that in the pulmonary artery nitric oxide plays a greater role in the modulation of baseline vascular tone and ACh-induced relaxation than in the celiac artery. In addition, cyclooxygenase products do not contribute to the direct contractile responses to L-NAME and L-NMMA in both the pulmonary and celiac artery rings but do modulate the ACh-induced relaxation of these vessels.
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PMID:Differential effect of nitric oxide synthase inhibitors on acetylcholine-induced relaxation of rat pulmonary and celiac artery rings. 919 53

Induction of anaesthesia with intravenous propofol and thiopental is often accompanied by hypotension. This study evaluates whether propofol and thiopental induce relaxation of isolated arteries from man and whether this effect is modulated by the endothelium. Mesenteric artery rings (with and without endothelium) from 12 patients were placed in organ baths and precontracted with phenylephrine before addition of propofol (10(-3) M) or thiopental (10(-3) M). Relaxation induced by propofol and thiopental was evaluated for rings with intact endothelium in the presence of the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10(-4) M) or the cyclooxygenase inhibitor indomethacin (10(-5) M). The vasodilator effect of propofol was similar for intact and denuded endothelium rings whereas the relaxation induced by thiopental was significantly attenuated in denuded-rings. In intact endothelium rings, L-NAME and indomethacin caused marked inhibition of the relaxation induced by thiopental, but not that induced by propofol. These results suggest that propofol induces endothelium-independent relaxation of isolated mesenteric arteries in man, whereas thiopental causes endothelium-dependent relaxation mediated by nitric oxide and prostaglandins.
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PMID:Role of the endothelium in the relaxation induced by propofol and thiopental in isolated arteries from man. 923 43

The roles of NO synthase (NOS) and cyclooxygenase on vascular pressures were studied as a function of sex and pregnancy. After anesthesia, mean arterial pressure (MAP) and mean circulatory filling pressure were lower in pregnant rats compared with male and virgin rats, but N(G)-nitro-L-arginine methyl ester (L-NAME; 30 mg/kg) induced similar increases in MAP. Pithing abolished these pressure differences, suggesting a diminished autonomic reflex in pregnancy, and led in pregnant rats to a lower arterial and venous NO modulation. In separately perfused mesenteries, the lower responses to KCI observed in venous beds of female compared with male rats do not involve any dysfunction of NOS activity in the mesenteries isolated from virgin and pregnant rats. The cyclooxygenase pathway is implicated in the KCl-induced responses of vessels taken from male rats and of venous mesentery from pregnant rats. But prostanoids do not share in the acetylcholine (ACh)-induced relaxations in the arterial and venous K+-contracted mesenteric vasculatures isolated from any of the groups of rats.
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PMID:Roles of NO-synthase and cyclooxygenase in sex- and pregnancy-dependent arterial and venous pressures in the rat. 926 48

Furosemide pretreatment greatly reduces the severity of an asthmatic response to several types of bronchoconstrictor challenge. Indirect evidence suggests that furosemide exerts its protective effects by dilating the airway vasculature during thermal stress. To test the hypothesis that furosemide dilates airway microvessels, the tracheas of anesthetized rats were surgically exposed and continuously suffused with Krebs Ringer bicarbonate warmed to 37 degrees C. Tracheal adventitial arterioles (13.0 to 41.0 microns initial diameter, n = 47) and venules (50.0 to 99.0 microns initial diameter, n = 46) were visualized with a videomicroscope, and vessel diameters were measured using videocalipers. When vessels were preconstricted with 10(-4) M phenylephrine, a selective alpha 1-adrenergic agonist, and then treated with 10(-4) M furosemide, significant (p < 0.05) dilation was observed in both arterioles (from 64.6 to 79.5% of their initial diameter) and venules (from 52.1 to 65.4% of their initial diameter). When vessels were preconstricted with 10(-4) phenylephrine, after pretreatment with the cyclooxygenase inhibitor indomethacin (5.0 mg/kg), 10(-4) M furosemide significantly dilated arterioles (from 77.5 to 93.0% of their initial diameter) and venules (from 58.5 to 80.1% of their initial diameter). In vessels preconstricted with 10(-3) M L-NAME, an inhibitor of nitric oxide synthesis, addition of 10(-4) M furosemide to the suffusion still caused significant dilation in arterioles, from 77.4 to 88.8% of their initial diameter, and in venules from 79.5 to 86.7% of their initial diameter. These data confirm that furosemide, when applied topically, dilates tracheal arterioles and venules by cyclooxygenase- and nitric oxide-independent mechanisms.
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PMID:Dilatory effect of furosemide on rat tracheal arterioles and venules. 927 27

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