Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endothelium-derived relaxing factor (EDRF) is a potent endogenous vasodilator that has been indirectly suggested to play a role in isoflurane-mediated vasodilation. To examine directly the possible role of EDRF in isoflurane-mediated vasodilation, isolated rat thoracic aortic rings were suspended for isometric tension measurements, equilibrated to a resting tension of 2 g, and constricted with a 50% maximal concentration (EC50) dose of phenylephrine or KCl. Three groups of rings were studied: endothelium-intact, endothelium-denuded, and endothelium-intact rings treated with nitro-L-arginine methyl ester (L-NAME), a specific inhibitor of EDRF synthase. Isoflurane was then added at 1, 2, and 3% in a cumulative manner, allowing 10 min for each concentration to equilibrate. Indomethacin was present in all experiments to prevent the formation of vasoactive prostanoid metabolites. Since EDRF causes vascular relaxation by stimulating soluble guanylyl cyclase and increasing cyclic GMP, the effect of isoflurane on vascular ring cyclic GMP content was determined as an additional indicator of EDRF-mediated dilation. Rings with intact and denuded endothelium were isolated as described above, constricted with phenylephrine, and challenged with methacholine (positive control) or 1, 2, or 3% isoflurane. After 8 min exposure, the rings were flash-frozen in dry-ice-cooled acetone and homogenized in 1 N HCl for subsequent analysis of cyclic GMP content by radioimmunoassay. Isoflurane caused dose-dependent vasodilation of both KCl- and phenylephrine-constricted rings. In the phenylephrine group, at 2% and 3% isoflurane, endothelium-denuded and L-NAME-treated rings relaxed to a greater extent than endothelium-intact rings (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Isoflurane does not vasodilate rat thoracic aortic rings by endothelium-derived relaxing factor or other cyclic GMP-mediated mechanisms. 131 21

1. The effect of intradermally injected endotoxin on skin blood flow was investigated in anaesthetized male Wistar rats in vivo. 2. Local skin blood flow changes were measured hourly for 6 h in the shaved dorsal skin with a laser-Doppler flow probe and compared to changes in control sites which had been injected with 100 microliters of phosphate-buffered saline. By 3 h, skin blood flow increased above basal by 129 +/- 27% and 186 +/- 29% with 1 and 10 micrograms of endotoxin respectively. Blood flow remained significantly elevated at 6 h, the corresponding figures being 129 +/- 24% and 154 +/- 31% (P less than 0.05, n = 6 rats, mean +/- s.e.mean). 3. In further experiments, the response to 3 micrograms of endotoxin was measured at 4 h and treatment with a cyclo-oxygenase inhibitor, nitric oxide synthase inhibitors or a topical steroid all significantly inhibited this response (P less than 0.05 in each case, n = 6 rats in each group with duplicate sites in each animal). 4. Indomethacin 3 x 10(-9) mol per site injected 3.5 h after injection of endotoxin suppressed the mean 4 h response to endotoxin by 78%; NG-nitro-L-arginine methyl ester (L-NAME) 10(-7) mol per site suppressed the response by 95%; NG-monomethyl-L-arginine (L-NMMA) 10(-7) mol per site suppressed the response by 50%; whereas the D-isomer of NG-monomethyl-arginine 10(-7) mol per site had no significant effect.5. Topical application of the corticosteroid, betamethasone 17-valerate (1% solution) 18 h before injection of endotoxin inhibited the mean 4 h response to endotoxin by 66% and the 6 h response by 48%.6. In the same model, the vasodilator response to arachidonic acid was inhibited by both indomethacin and nitric oxide synthase inhibitors (P<0.05 in each case).7. These data suggest that the microcirculatory vasodilator response to endotoxin and arachidonic acid injected locally involves both nitric oxide synthase and cyclo-oxygenase in this in vivo model.
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PMID:Endotoxin-induced vasodilatation in anaesthetized rat skin involves nitric oxide and prostaglandin synthesis. 138 90

1. The possible participation of prostacyclin and nitric oxide (NO) in the gastric mucosal hyperaemic response to acid back-diffusion through a disrupted gastric mucosal barrier was examined. The experiments were carried out on anaesthetized rats in which acid back-diffusion was elicited by gastric perfusion with dilute ethanol in 0.15 M HCl and gastric mucosal blood flow (MBF) was measured by the hydrogen gas clearance technique. 2. Indomethacin (28 mumols kg-1, s.c.), an inhibitor of the formation of cyclo-oxygenase products including prostacyclin, failed to alter mean arterial blood pressure (MAP), basal MBF and the hyperaemic response to acid back-diffusion in urethane-anaesthetized rats. 3. NG-nitro-L-arginine methyl ester (L-NAME; 13 and 43 mumols kg-1, i.v.), an inhibitor of endothelium-derived NO formation, increased MAP in a dose-dependent manner. Whilst basal MBF in urethane-anaesthetized rats was not changed, the increase in MBF caused by gastric perfusion with dilute ethanol in acid was dose-dependently depressed by L-NAME. The loss of H+ ions from the gastric lumen, an indirect measure of acid back-diffusion, was significantly enhanced by 43 mumols kg-1 L-NAME. In contrast, D-NAME (13 and 43 mumols kg-1) was without effect on MAP, basal and stimulated MBF, and acid back-diffusion. 4. Unlike in urethane-anaesthetized rats, L-NAME led to a significant reduction of basal MBF in phenobarbitone-anaesthetized rats. MAP in the phenobarbitone-anaesthetized rats was significantly higher than in urethane-anaesthetized rats, and the hypertensive effect of L-NAME under phenobarbitone anaesthesia was significantly smaller than under urethane anaesthesia.5. The rise in MBF brought about by acid back-diffusion was blocked by L-NAME administered to phenobarbitone-anaesthetized rats. Infusion of L-arginine (120 pmol kg -1 min- ', i.v.) led to a partial, but significant, reversal of the effects of L-NAME on MAP and the hyperaemia due to acid back-diffusion.6. These findings indicate that endothelium-derived NO plays an important mediator role in the gastric mucosal vasodilatation caused by back-diffusion whilst vasodilator prostanoids such as prostacyclin are not involved.
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PMID:Participation of endothelium-derived nitric oxide but not prostacyclin in the gastric mucosal hyperaemia due to acid back-diffusion. 162 57

1. Measurements of changes in renal, mesenteric and hindquarters haemodynamics or cardiac haemodynamics in response to i.v. bolus doses of arginine vasopressin (AVP) or lysine vasopressin (LVP, 0.7 and 7.0 pmol) were made in conscious, chronically-instrumented Long Evans rats. 2. In some experiments AVP and LVP were administered during an infusion of NG-nitro-L-arginine methyl ester (L-NAME; 1.0 or 0.3 mg kg-1 h-1) to determine whether or not inhibition of nitric oxide production influenced the cardiovascular effects of the peptides. In other experiments, indomethacin (bolus dose of 5 mg kg-1 followed by infusion at 5 mg kg-1 h-1) was given to determine the possible involvement of cyclo-oxygenase products in the responses to AVP and LVP. 3. Under control conditions, the lower dose of LVP had significantly greater effects than AVP on heart rate, mean arterial blood pressure, renal, mesenteric and hindquarters conductances, total peripheral conductance, cardiac index, peak aortic flow and +dF/dtmax. The higher dose of LVP had significantly greater effects than AVP on all variables (i.e. including stroke index and central venous pressure). 4. In the presence of L-NAME (1 mg kg-1 h-1) there was a sustained increase in mean arterial blood pressure (+23 +/- 3 mmHg) and reductions in mesenteric (-38 +/- 4%) and hindquarters (-30 +/- 6%) vascular conductances. Under these conditions the difference in the pressor effects of AVP and LVP was abolished, but their differential effects on regional and cardiac haemodynamics persisted. This dose of L-NAME did not change cardiac baroreflex sensitivity. 5. During infusion of L-NAME at a lower rate (0.3mgkg-th-1), baseline cardiovascular status was unchanged and regional haemodynamic effects of AVP and LVP were enhanced, but the differences in the regional vasoconstrictor responses to the two peptides persisted. 6. Indomethacin (5 mg kg-1 bolus, then 5 mg kg- 'h-1 infusion) augmented the renal vasoconstrictor responses to AVP and LVP, but abolished the difference in the hindquarters vasoconstrictor responses to the two peptides. However, the differences in the pressor and the renal and mesenteric vasoconstrictor effects of AVP and LVP still occurred in the presence of indomethacin. 7. The results indicate that AVP normally has lesser cardiovascular effects than LVP but this difference does not seem to be due to more effective stimulation of nitric oxide-mediated or cyclo-oxygenase-dependent vasodilator mechanisms by AVP than LVP.
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PMID:Effects of NG-nitro-L-arginine methyl ester or indomethacin on differential regional and cardiac haemodynamic actions of arginine vasopressin and lysine vasopressin in conscious rats. 204 32

Ischemia and reperfusion have been shown to cause damage to the endothelium as well as to the cardiac myocyte. Although the vasodilator response has been shown to be impaired following ischemia and reperfusion, the effect of a short period of global ischemia on the contractile response of the coronary vasculature is not clear. In the present study, coronary vasoconstriction in response to U46619, PGF2 alpha, 5-HT, and KCl was found to be depressed for at least 15 min following 15 min of in vitro global ischemia in rats hearts. Vasodilator blockers or inactivators were used in an effort to restore this depressed coronary response. Indomethacin (5 microM) was used to block production of vasodilator prostaglandins, L-NAME (30 microM) to block production of nitric oxide (NO), and adenosine deaminase (2.4 units/ml of coronary flow) to inactivate adenosine. None of these agents restored the normal coronary constrictor response following ischemia. When superoxide dismutase and catalase (both 20 micrograms/ml of coronary flow) were infused for 5 min before and after ischemia, the coronary response recovered more than 100% of its preischemic value by 15 min of reperfusion, but still remained depressed at 5 min reperfusion. These data suggest that free radicals produced during ischemia and/or reperfusion may be at least partly responsible for this temporary "stunning" of the coronary vasculature. Since the impaired contractile response was still present at 5 min reperfusion when the buffer was supplemented with oxygen radical scavengers, another mechanism must also be involved in this "stunning" process.
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PMID:Effects of short term ischemia and reperfusion on coronary vascular reactivity and myocardial function. 747 69

The present study was designed to investigate the contribution of the endothelium and that of the L-arginine pathway on the contractile responses of isolated human pulmonary arteries to electrical field stimulation (EFS) and noradrenaline. Isometric tension was measured in artery rings obtained from portions of human lung after thoracic surgery for removal of lung carcinoma (18 patients). Electrical field stimulation (EFS) induced frequency-dependent contractions of isolated human pulmonary arteries which were abolished by tetrodotoxin, guanethidine and prazosin (all at 10(-6) M). The increases in tension were of greater magnitude in arteries denuded of endothelium. NG-nitro-L-arginine methyl ester (L-NAME) (10(-4) M) potentiated the contractile response to EFS in artery rings with endothelium but not in endothelium-denuded arteries. The potentiation induced by L-NAME was completely reversed by L-arginine (10(-4) M) but not by D-arginine (10(-4) M). Indomethacin (3 x 10(-6) M) had no significant effect on the contractile response to EFS. Contractile responses to noradrenaline were similar in arteries with and without endothelium. Our results suggest that electrical field stimulation releases endothelium-derived nitric oxide, which inhibits the contractile responses of human pulmonary arteries. Although adrenergic nerves seem to be responsible for the contraction, the transmitter involved in the release of nitric oxide does not appear to be noradrenaline.
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PMID:Influence of endothelial nitric oxide on neurogenic contraction of human pulmonary arteries. 748 99

The actions of NO synthase inhibitors and indomethacin, a cyclooxygenase inhibitor, on the nonadrenergic noncholinergic (NANC) mechanical responses of cat distal colon were studied in vitro using muscle strips orientated in the axis of the longitudinal muscle layer with pelvic nerves attached. Electrical field stimulation (EFS) or pelvic nerve stimulation (PNS) caused inhibition of spontaneous contractions followed by off-contractions. Indomethacin (10-30 microM) caused concentration-dependent reductions in amplitude and duration of EFS- and PNS-evoked off-contractions but not latency. The NO synthase inhibitors, N omega-nitro-L-arginine (L-NNA), N omega-nitro-L-arginine methyl ester (L-NAME) and NG-monomethyl-L-arginine (L-NMMA) (each at 100 microM) significantly reduced latency, amplitude, and duration of off-contractions evoked by EFS and PNS. This inhibition was partially reversed by L-arginine (120 microM) but not by D-arginine. Incubation of colonic strips with alpha-chymotrypsin (2 U/ml) decreased latency, amplitude, and duration of NANC off-contractions. L-NNA reduced amplitude, duration, and latency of off-contractions in preparations pretreated with alpha-chymotrypsin. Hydroquinone (10-30 microM), a generator of superoxide anions, caused significant depression of amplitude, duration, and latency of off-contractions which was completely reversed by superoxide dismutase (200 U/ml). These data suggest that the components of NANC off-contractions evoked by EFS and PNS involve peptides, NO, and prostaglandins.
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PMID:A nitric oxide and prostaglandin-dependent component of NANC off-contractions in cat colon. 750 99

The effects of endothelin-1 (ET-1), an ET(A)/ETB-receptor agonist, and IRL 1620, a potent and selective ETB-receptor agonist, were assessed on left circumflex coronary artery diameter (sonomicrometry) and flow (electromagnetic flow probe) in pentobarbital-anesthetized dogs. Intracoronary (i.c.) bolus injections of ET-1 (80 pmol/dose) caused large, sustained coronary diameter decreases (281 +/- 39 microns) and transient flow increases (5.6 +/- 2.6 ml/min), followed by transient (10.0 +/- 1.9 ml/min) and then sustained flow reductions (6.6 +/- 2.5 ml/min) before terminating in ventricular fibrillation after two to five doses (max delta s; n = 4 dogs). IRL 1620 boluses (5-2,000 pmol/dose i.c.; max delta s; n = 3) also dose-dependently and transiently increased (16.8 +/- 1.4 ml/min; 200 pmol), then transiently decreased (12.8 +/- 1.5 ml/min; 1,600 pmol) flow but had minimal effects on diameter (delta = -23 +/- 4 microns; 2,000 pmol). Doses of IRL 1620 beyond 400 pmol were accompanied by a slowly responding, sustained decrease in baseline flow (-9.2 +/- 2.7 ml/min) and baseline diameter (232 +/- 150 microns). In a separate group of dogs (n = 5), IRL 1620 (400 pmol i.c.) was evaluated before and after sequential inhibition of cyclooxygenase (indomethacin; 10 mg/kg i.v.) and then nitric oxide synthase (N omega-nitro-L-arginine methyl ester, L-NAME; 50 mg/kg i.v.). Indomethacin alone did not affect the flow increase to IRL 1620 (11.0 +/- 2.0 versus 11.8 +/- 1.8 ml/min) but blunted the flow decrease by 30 +/- 6% (10.6 +/- 1.4 versus 7.1 +/- 0.7 ml/min).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential responsiveness of conduit and resistance coronary arteries to endothelin A and B receptor stimulation in anesthetized dogs. 750 56

We determined the effects of human basic fibroblast growth factor (bFGF) on blood pressure (BP) and heart rate (HR) in pentobarbital-anesthetized rats and examined the possible involvement of nitric oxide (NO) and prostanoids in these effects. Intravenous (i.v.) injections of bFGF (1, 7.5, and 15 micrograms/kg) induced dose-dependent short-lasting decreases in BP followed by a striking increase in BP and HR variability. The BP and HR increases in variability were closely related (r = 0.95; n = 20; p < 0.001). Pretreatment with a single intravenous (i.v.) dose of N omega-nitro-L-arginine methyl ester (L-NAME, 20 mg/kg) almost suppressed (-90%) the cardiovascular effects of bFGF, an effect that was restored by a single dose of L-arginine (100 mg/kg i.v.). Similar suppression was observed with use of indomethacin (10 mg/kg i.v.). Indomethacin given 50-60 min after bFGF abolished the increased variability of BP and HR. We conclude that the BP decrease and the increase in BP and HR variability induced by bFGF involve release of both NO and vasoactive prostanoids.
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PMID:Cardiovascular effects of basic fibroblast growth factor in rats. 751 43

Careful handling and preparation of freshly harvested vessels from 22 pigs and 12 rabbits revealed a two-phase vasorelaxation response to cumulative doses of substance P (SP). A rapid, transient relaxation was observed during the cumulative dose-response and a new plateau of equilibrium was seen following an increase in developed force after the last dose of SP. The phase 2 response is also produced by submaximal doses of SP and is not altered by pretreatment of the rings with Indomethacin. Acetylcholine (ACh) caused an endothelium-dependent relaxation but without evidence of a phase 2 plateau. N omega-Nitro-L-Arginine (L-NNA) and N omega-Nitro-L-Arginine Methylester (L-NAME) pretreatment resulted in a shift to the right in the phase 1 response to SP and a complete blockade of phase 2. Methylene blue caused nearly complete block of both phases. Nitroglycerin caused a dose-dependent and prolonged vasorelaxation with no phase 2.
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PMID:Substance P induces biphasic endothelium-dependent relaxations in pig and rabbit carotid arteries. 752 May 54


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