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)

Leptin is a polypeptide, mainly produced in white adipose tissue, and increases sympathetic nerve activity. A few studies investigated leptin's effect on peripheral vessels. We examined the vasorelaxant effects of human leptin on rat arteries. Arterial rings were precontracted with 1 x 10(-6) mol/l of phenylephrine, and leptin was superfused. Leptin relaxed phenylephrine-precontracted arterial rings in a dose-dependent manner. ED50 was calculated to 8.4 microg/ml. Removal of endothelium abolished the effects of leptin. Indomethacin (1 x 10(-5) mol/l) did not affect the vasorelaxation by leptin, whereas 1 x 10(-4) mol/l of N(omega)-nitro-L-arginine methyl ester (L-NAME) completely suppressed it. The inhibition was antagonized by 1 x 10(-4) mol/l of L-arginine. Leptin normally relaxed arterial rings during superfusion of K channel blockers, including 3 x 10(-5) mol/l of glibenclamide, 1 x 10(-6) of mol/l apamin, and 5 x 10(-7) mol/l of charybdotoxin. Low Cl(-) solution (8. 3 mmol/l) inhibited leptin-induced relaxation, but endothelium-independent vasodilatation by nitroprusside was not impaired at low Cl(-) solution. These results suggest that arterial relaxation by leptin is mediated by nitric oxide released from endothelium, and Cl(-) plays an important role in leptin-induced nitric oxide release.
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PMID:Involvement of nitric oxide in endothelium-dependent arterial relaxation by leptin. 1087 74

After abdominal surgery, luminal HCl fails to induce duodenal contractions in anaesthetized rats. Elevated tissue levels of nitric oxide (NO) and prostaglandins possibly contribute to this observation. The aim of this study was to compare the effects of luminal capsaicin (1.2 mg mL-1), ethanol (15%) and high partial pressure of CO2 (>250 mmHg) with those of HCl (10 mM) in anaesthetized rats. Motility (intraluminal pressure), mucosal permeability [blood-to-lumen clearance of 51Cr-EDTA (51Chromium-labelled ethylenediaminetetraacetate)] and duodenal mucosal bicarbonate secretion (DMBS) were recorded. Three groups of animals were studied: (1) controls, (2) pretreatment with the NO synthase inhibitor N-nitro-L-arginine-methyl-ester (L-NAME) and (3) pretreatment with the cyclo-oxygenase inhibitor indomethacin. Neither capsaicin, ethanol, CO2 nor HCl induced duodenal contractions or affected DMBS in control rats. However, L-NAME induced duodenal contractions that were augmented by capsaicin, ethanol and HCl, but not by CO2. Indomethacin also induced contractions that were reversibly diminished by capsaicin and HCl, but not by ethanol or CO2. Significant increases in mucosal permeability occurred during ethanol perfusion in indomethacin- and L-NAME pretreated rats. In conclusion, NO probably plays a key role in preventing duodenal contractions in response to luminally HCl, capsaicin and ethanol. The HCl-induced effect on motility appears to be independent of CO2 and is not caused by alteration in mucosal integrity.
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PMID:Nitric oxide prevents rat duodenal contractions induced by potentially noxious agents. 1088 38

We have previously reported a significant contribution of ET(A)- and ET(B)-receptors in the eicosanoid-releasing properties of endothelin-1 (ET-1) in the guinea-pig perfused lung. More recently, it was found that intravenously administered ET-1 in the guinea-pig triggers the release of hypotensive and bronchoconstrictive eicosanoids which is strongly modulated by endogenous nitric oxide. In this study we investigate the contribution of both ET receptors as well as of the eicosanoids and nitric oxide to the vasoconstrictor properties of ET-1 in the guinea-pig kidney. The kidney was isolated from stunned and spinal cord-sectioned guinea-pig (300-350 g) and rapidly suspended and perfused (3 ml/min) with oxygenated Krebs solution at 37 degrees C. ET-1 (1-1000 pmol) induced dose-dependent increases in perfusion pressure in the perfused guinea-pig kidney. Furthermore, the pressor effect of a dose of ET-1 (40 pmol) was markedly reduced after a 15-min infusion of the ET(A) antagonist, BQ-123 (1 microM). The ET-1-induced vasoconstriction was restored 50 min after the cessation of BQ-123 infusion. In contrast, the selective ET(B)-receptor agonist, IRL-1620 (1-1000 pmol) was found to be inactive. Indomethacin (5 microM) and the ET(B)-receptor antagonist, BQ-788 (10 nM) did not affect the constrictor effect of ET-1. The infusion of ET-1 (0.5 and 1 microM, 5 min) in the guinea-pig kidney did not induce the release of prostacyclin or thromboxane. Finally, a 60 min infusion with the nitric oxide synthase inhibitor, L-NAME (200 microM) markedly potentiated the constrictor effects of ET-1. Our results suggest that unlike the pulmonary vasculature, the guinea-pig kidney responds to ET-1 by a direct constriction, which is modulated by nitric oxide but not eicosanoids (supported by the MRCC).
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PMID:Endothelin-1 induces an endothelin-A-receptor-dependent and L-NAME-sensitive vasoconstriction in the isolated perfused guinea-pig kidney. 1107 87

Endothelin-1 (ET-1) produces potent renal effects that we have previously shown to be dependent on cytochrome P-450 (CYP450) metabolites of aracidonic acid (24) This study evaluated the role of these metabolites in the effects produced by ET-1 on renal blood flow (RBF), cortical blood flow (CBF), medullary blood flow (MBF), and mean arterial blood pressure (MBP). ET-1 (20-200 pmol/kg) increased MBP, renal vascular resistance (RVR), and MBF but reduced CBF and RBF in a dose-dependent manner. The decreases in CBF and RBF, and increases in MBP and RVR were blunted by BMS-182874, an ET(A) receptor antagonist or BQ-788, an ET(B) receptor antagonist. Similarly, indomethacin, an inhibitor of cyclooxygenase activity, or 12,12-dibromododecenoic acid (DBDD), a CYP450-dependent inhibitor of production of 20-hydroxyeicosatetraenoic acid (20-HETE), blunted these effects. ET-3 elicited dose-related reduction in CBF and increase in MBF. Indomethacin accentuated the reduction in CBF and attenuated the increase in MBF, as did DBDD. ET-1-induced increase in MBF was attenuated by BQ-788, N(omega)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide (NO) synthesis, indomethacin, or DBDD. DBDD inhibited the hemodynamic effects of L-NAME. Miconazole, the inhibitor of CYP450-dependent epoxygenase activity, was without effect. These results indicate that hemodynamic changes produced by ET-1 are mediated by vasoconstrictor prostanoids and/or prostanoid-like substances, possibly, 20-HETE via activation of ET(A) and ET(B) receptors. However, the increase in MBF is mediated by vasodilator prostanoids or by NO via ET(B) receptor activation.
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PMID:Role of NO and cytochrome P-450-derived eicosanoids in ET-1-induced changes in intrarenal hemodynamics in rats. 1108 78

Resveratrol has been shown to induce vasorelaxation. In this study, we investigated the mechanism(s) of resveratrol-induced vasorelaxation in resistance mesenteric arteries from male lean and dietary-induced obese rats. Compared with lean rats, arteries from dietary-obese rats showed significant (P<0.001) endothelial dysfunction, as indicated by a decrease (>20%) in maximal acetylcholine-induced vasorelaxation. Resveratrol (5-35 micromol/l) induced concentration-dependent relaxation of mesenteric arteries preconstricted with noradrenaline (8 micromol/l) or KCl (125 mmol/l) from both lean and dietary-obese rats. There were no significant differences between the two groups, achieving a maximum relaxation of >95% at a concentration of 35 micromol/l. In noradrenaline-preconstricted arteries from lean rats, N(G)-nitro-L-arginine methyl ester (L-NAME; 100 and 300 micromol/l) caused a significant (P<0.01) concentration-dependent rightward shift in reseveratrol activity, with no effect on maximal responses. However, L-NAME (100 and 300 micromol/l) did not alter the effects of reseveratrol on arteries from dietary-obese rats, giving superimposed concentration-responses curves. Indomethacin was also ineffective in altering resveratrol activity in arteries from both lean and dietary-obese rats. In noradrenaline-precontracted arteries from dietary-obese rats, responses to resveratrol were not attenuated by endothelial denudation, indicating an action independent of the endothelium. This study indicates that: (a) the maximal effects of resveratrol on resistance arteries from lean and dietary-obese rats are not effected by endothelial dysfunction, and (b) the effects of resveratrol in lean animals (where endothelial function is not impaired), but not in dietary-obese rats, are mediated via NO.
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PMID:The mechanism of resveratrol-induced vasorelaxation differs in the mesenteric resistance arteries of lean and obese rats. 1111 18

The aim of the study was to evaluate the effect of losartan on rat platelet adhesion to fibrillar collagen. Washed platelets were counted before and after 15 minutes incubation with collagen (50 microg/ml) and the percentage of adhering platelets was calculated as the index of their adhesion. When the platelets were incubated with collagen 40.8 +/- 0.3% of the platelets adhered. Losartan produced a dose dependent decrease in a number of adhering platelets both when the drug was administered to the animals ex vivo at doses of 3, 10 and 30 mg/kg (p < 0.01-0.001) or was added to the preparation of washed platelets in vitro in concentrations of 10(-8)-10(-5) M (p < 0.01-0.001). In the next step of the study we assessed the influence of L-NAME (10 mg/kg ex vivo, 30 microM in vitro) and indomethacin (2.5 mg/kg ex vivo, 30 microM in vitro) on the antiadhesive effect of losartan (10 mg/kg ex vivo, 10(-6) M in vitro). Blockade of nitric oxide synthase with L-NAME partially reversed the antiadhesive effect of losartan both ex vivo and in vitro. Indomethacin diminished the inhibitory effect of losartan on platelet adhesion when administered ex vivo, but it failed to modify this parameter when added to the suspension of platelets in vitro. In conclusion, losartan reduces platelet adhesion to fibrillar collagen in a dose-dependent manner. The observed action of losartan seems to be mediated mainly by endothelium- and platelet-derived nitric oxide.
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PMID:Losartan inhibits the adhesion of rat platelets to fibrillar collagen--a potential role of nitric oxide and prostanoids. 1119 43

1. Protease activated receptor-2 (PAR2) is a seven transmembrane domain G protein coupled receptor proteolytically activated. PAR2, together with other PARs, can be also activated by peptides mimicking the sequence of the receptor tethered ligand. We have evaluated the effect of systemic administration of a peptide activating PAR2 (PAR2-AP, SLIGRL) on histamine-induced increase in lung resistances in the guinea-pig. 2. Intravenous administration of PAR2-AP (1 mg kg(-1)) significantly inhibited histamine-induced increase in lung resistance in a time-dependent fashion that was not abolished by indomethacin or vagotomy. 3. Bronchoprotective effect of PAR2-AP was not reversed by the cyclo-oxygenase inhibitor, indomethacin, the nitric oxide synthetase inhibitor, L-NAME, nor by the non-selective beta-antagonist, propranolol. 4. Indomethacin augmented the bronchoconstriction to histamine which was inhibited by PAR2-AP. Furthermore, in vagotomized animals, the bronchial hyper-responsiveness to histamine was significantly reduced, and in these circumstances, PAR2-AP still retained the capacity to provide bronchoprotection against histamine. 5. PAR2-AP also produced a modest reduction in histamine-induced protein leakage in trachea and upper bronchi. 6. Our results indicated that PAR2 might have a bronchoprotective role in the guinea-pig in vivo independent of prostaglandin or nitric oxide release.
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PMID:Protective effect of a PAR2-activating peptide on histamine-induced bronchoconstriction in guinea-pig. 1125 Aug 73

The pathogenesis of radiocontrast nephropathy is poorly understood. In an animal model, inhibition of the synthesis of nitric oxide and prostaglandins appears to predispose rats to severe renal injury following the administration of radiocontrast. Here we have investigated whether administration of radiocontrast, as well as changes in renal medullary oxygenation following pharmacologic inhibition of nitric oxide and prostaglandin synthesis, might be evaluated by blood oxygenation level-dependent (BOLD) MRI. Nineteen anesthetized (Inactin 100 mg/kg) rats were studied. BOLD MRI measurements were performed following administration of L-NAME (N-nitro-L-arginine methyl ester, 10 mg/kg), Indomethacin (10 mg/kg), and a radiocontrast agent (sodium iothalamate 60%, 6 mL/kg). Marked sequential changes in medullary R(*)(2), presumably reflecting decline in medullary pO(2), were noted after each of the pharmacological interventions employed. These results, obtained by noninvasive MRI, are consistent with prior direct recordings of pO(2) and doppler flow in the rat renal medulla after administration of L-NAME, Indomethacin and iothalamate. Medullary oxygenation in rats was reduced by inhibition of the synthesis of prostaglandins and nitric oxide, as well as by intravenous injection of radiocontrast agents. BOLD MRI can noninvasively evaluate changes in medullary oxygenation in rats that appear to predispose acute renal failure. J. Magn. Reson. Imaging 2001;13:744-747.
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PMID:Changes in intrarenal oxygenation as evaluated by BOLD MRI in a rat kidney model for radiocontrast nephropathy. 1132 96

Flow-induced dilation of gracilis muscle arterioles was examined in both genders of control rats and rats chronically treated with N(omega)-nitro-L-arginine methyl ester (L-NAME). After L-NAME treatment (4 wk), systolic blood pressure was significantly increased compared with control, whereas the plasma concentration of nitrate/nitrite was significantly reduced. Isolated and pressurized arterioles dilated significantly in response to increases in flow (0-25 microl/min). Flow-induced dilation was comparable in arterioles of control and L-NAME-treated rats but was significantly greater in female than in male rats. L-NAME + indomethacin, which abolished flow-induced dilation in arterioles of male control rats, inhibited the dilation by only ~75% in female control rats. The residual portion of the response was eliminated by additional administration of miconazole, an inhibitor of cytochrome P-450. Indomethacin did not affect the dilation in female L-NAME-treated rats but completely inhibited the response in male L-NAME-treated rats. The indomethacin-insensitive, flow-induced dilation in female L-NAME-treated arterioles was abolished by miconazole, 6-(2-proparglyoxyphenyl)hexanoic acid, or charybdotoxin. Thus an augmented release of endothelial prostaglandins accounts for the preserved flow-induced dilation in arterioles of male rats, whereas a metabolite of cytochrome P-450 is responsible for the maintenance of flow-induced dilation in female rats, suggesting important differences in the adaptation of the endothelium of arterioles from male and female rats to the lack of nitric oxide (NO) synthesis.
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PMID:Gender-specific compensation for the lack of NO in the mediation of flow-induced arteriolar dilation. 1135 98

Duodenal HCO3- secretion increases in response to mucosal acidification by luminal acid. Although this process is known to be mediated by endogenous prostaglandins (PGs), the role of nitric oxide (NO) in this response has been little studied. We examined the effects of indomethacin and N(G)-nitro-L-arginine methyl ester (L-NAME) on the acid-induced HCO3- secretion in the rat duodenum, together with those on PGE2 generation as well as luminal release of NO metabolites (NOx). A proximal duodenal loop was perfused with saline, and the HCO3- secretion was measured at pH 7.0 using a pH-stat method and by adding 10 mM HCl. Mucosal acidification was performed by exposing the loop to 10 or 100 mM HCl for 10 min. Acidification of the duodenal mucosa stimulated the HCO3- secretion, with concomitant increase of mucosal PGE2 contents and luminal release of NOx, the response being much greater in case of 100 mM HCl. Indomethacin significantly inhibited the acid-induced HCO3- secretion as well as the PGE2 biosynthetic response, without influence on the NOx release. Pretreatment of the animals with L-NAME attenuated both the increase of mucosal PGE2 contents and luminal release of NOx following the acidification, resulting in a marked inhibition of the acid-induced HCO3- response, and these effects were significantly antagonized by coadministration of L-arginine. Duodenal HCO3- secretion was also increased by mucosal exposure to NOR-3 (a NO donor), with concomitant increase of PGE2 generation, but these effects were mitigated in the presence of indomethacin. In addition, the duodenal damage caused by mucosal perfusion with 100 mM HCl for 4 hr was markedly aggravated by pretreatment with L-NAME as well as indomethacin. These results suggest that both endogenous NO and PGs are involved in the mechanism for the acid-induced duodenal HCO3- secretion, and that NO may increase the HCO3- secretion by stimulating PG generation.
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PMID:Role of endogenous nitric oxide and prostaglandin in duodenal bicarbonate response induced by mucosal acidification in rats. 1141 96

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