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)

1. The vasoconstrictor effects of noradrenaline applied to the intimal and adventitial surfaces of perfused segments of rat tail artery in the presence and absence of endothelium were studied. 2. Noradrenaline was about six times more potent as a vasoconstrictor when applied to the intimal than to the adventitial surface. Cocaine (25 mumol/L) enhanced responses to adventitial noradrenaline to a greater extent than those to intimal noradrenaline. A high concentration of propranolol (1 mumol/L) had a similar effect. 3. The vasoconstriction elicited by adventitial noradrenaline declined from a peak whereas that to intimal noradrenaline remained steady. A low concentration of propranolol (0.1 mumol/L) abolished the decline in the response to adventitial noradrenaline. 4. The alpha 1- and alpha 2-adrenoceptor antagonists prazosin (1 nmol/L) and idazoxan (100 nmol/L) significantly reduced responses to intimal and adventitial noradrenaline in the presence or absence of endothelium. 5. Removal of endothelium enhanced responses to intimal but not adventitial noradrenaline. Idazoxan produced a significantly greater reduction of responses to noradrenaline in the absence than in the presence of endothelium, and was more effective against intimal than adventitial noradrenaline. Similar effects were produced by the nitric oxide synthase inhibitor L-NAME (30 mumol/L). 6. It was concluded that noradrenaline acts on both alpha 1- and alpha 2-adrenoceptors to produce vasoconstriction: the alpha 1-adrenoceptors appear to be uniformly distributed, whereas alpha 2-adrenoceptors are located nearer the intima. Intimal noradrenaline also acts on endothelial alpha 2-adrenoceptors to release EDRF which counteracts the vasoconstrictor action of noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Differential activation of adrenoceptor subtypes by noradrenaline applied from the intimal or adventitial surfaces of rat isolated tail artery. 790 97

We investigated the relative contribution of basal and agonist stimulated EDRF/NO release to the adjustment of coronary tone and myocardial perfusion in conscious dogs by inhibiting coronary endothelial NO formation with NG-nitro-L-arginine methyl ester (L-NAME). Chronically instrumented conscious dogs (n = 9) were prepared for measurement of mean arterial blood pressure (MAP), heart rate (HR), coronary blood flow (CF) and diameter of the left circumflex (CDLC) and left anterior descending (CDLAD) coronary artery, respectively. Intracoronary infusions of L-NAME (30.3 mM; 0.25 ml x min-1) caused significant increases in MAP and decreases in HR. CDLC decreased by 3.8% from 3.01 +/- 0.04 to 2.90 +/- 0.04 mm and CF decreases by 30% from 12.9 +/- 0.2 to 9.1 +/- 0.2 (aU). Peak reactive hyperemia (CFmax) evoked by 20-s-lasting occlusions of the left circumflex coronary artery decreased from 29.9 +/- 0.8 to 25.8 +/- 1.0 aU and maximal flow-dependent coronary dilation were reduced from 2.04 +/- 0.08 to 0.91 +/- 0.12% after inhibition of NO-synthesis. Intracoronary infusions of acetylcholine (ACh), adenosine (Ado), bradykinin (Bk), and papaverine (Pap) caused dose-dependent increases in CDLC and CF. Infusion of L-NAME nearly abolished the dilator effect of Ado on CDLC and reduced those to ACh, Bk and Pap. Increases in CF to ACh, Ado and Bk but not to Pap were reduced by L-NAME. Subsequent intracoronary infusions of L-arginine (303 mM; 0.25 ml x min-1) reduced L-NAME-induced CF-changes partly, but did not reverse coronary constriction. These results suggest that inhibition of the continuous release of nitric oxide markedly reduces myocardial perfusion in vivo.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reduced nitric oxide formation causes coronary vasoconstriction and impaired dilator responses to endogenous agonists and hypoxia in dogs. 791 78

The aim of this study was to examine the influence of vascular endothelium on the relaxation induced by increased extracellular Mg2+ concentrations on isolated and noradrenaline-precontracted aorta from deoxycorticosterone acetate-salt (DOCA-salt) hypertensive and normotensive rats. In Mg(2+)-free physiologic salt solution (PSS), addition of Mg2+ (0.1-6.0 nM) caused concentration-dependent relaxation of noradrenaline-precontracted aorta with intact or disrupted endothelium. Mg(2+)-induced relaxation in intact aorta, however, was less in DOCA-salt hypertensive rats than in normotensive rats. When endothelium was disrupted, Mg(2+)-induced relaxation was depressed in aorta from both DOCA-salt hypertensive and normotensive rats. The same observations were made in presence of N-nitro-L-arginine methyl ester (L-NAME), an inhibitor of endothelium-derived relaxing factor nitric oxide (EDRF/NO) biosynthesis. Mg(2+)-induced relaxation following contraction with noradrenaline was significantly less in intact aorta treated with L-NAME from DOCA-salt hypertensive rats than in intact aorta from normotensive rats. Indomethacin did not affect Mg(2+)-induced relaxation in intact aorta from normotensive rats whereas indomethacin significantly increased it in DOCA-salt hypertensive rats. It is concluded that (1) Mg(2+)-induced relaxation can be mediated by endothelium-dependent mechanisms implicating EDRF/NO; (2) the influence of EDRF/NO is more pronounced on the impaired Mg(2+)-induced relaxation of aorta from DOCA-salt hypertensive rats; (3) Mg(2+)-induced relaxation seems masked by vasoconstrictor prostaglandin release in DOCA-salt hypertensive rats; (4) these differences between normotensive and hypertensive rats could be related to the impaired endothelial function in aorta from DOCA-salt hypertensive rats.
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PMID:Influence of endothelium on Mg(2+)-induced relaxation in noradrenaline-contracted aorta from DOCA-salt hypertensive rat. 808 52

Endothelium-derived relaxing factor-nitric oxide (EDRF-NO) has been studied in isolated, pulmonary resistance vessels from term fetal lambs at a fetal (21 +/- 0.2 mmHg) and neonatal (69 +/- 0.4 mmHg) PO2. Bradykinin dose dependently (0.1-100 nM) relaxed arteries and veins that had been precontracted with a thromboxane A2 analogue. Their response did not differ at low PO2, whereas the response of the arteries was greater at high PO2. Sodium nitroprusside was almost as potent as bradykinin on the arteries, but its action did not vary with PO2. Acetylcholine also relaxed the arteries at higher concentrations (0.1-100 microM). N omega-mono-methyl-L-arginine (L-NMMA) and N omega-nitro-L-arginine methyl ester (L-NAME) (both at 100 microM) weakly contracted arteries at low PO2. The contraction to L-NAME, but not L-NMMA, increased with the PO2. In the arteries, L-NAME had no effect on bradykinin relaxation at low PO2, whereas it was an inhibitor at high PO2. Conversely, L-NMMA slightly inhibited bradykinin relaxation regardless of PO2. In the veins, L-NAME transiently increased basal tone and inhibited bradykinin relaxation at either PO2. Indomethacin (2.8 microM) had no effect on arteries at low PO2, whereas it was a constrictor at high PO2. No indomethacin constriction occurred in the veins. We conclude that fetal pulmonary resistance vessels possess an EDRF-NO relaxing mechanism that is stimulated by bradykinin. In the arteries, this mechanism is more effective at high PO2.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:EDRF in pulmonary resistance vessels from fetal lamb: stimulation by oxygen and bradykinin. 816 Aug 41

Nonlinear mathematical techniques now make it possible to quantify the complexity of an irregular time series through calculation of a parameter known as fractal dimension. In the present study, we use such an analysis to provide evidence that histamine-induced pressure oscillations in an isolated rabbit ear resistance artery are generated by deterministic rather than stochastic mechanisms, and that a minimum of 3 independent control variables is necessary to account for the complexity of the dynamics of these oscillations. The fractal dimension of the responses was independent both of the concentration of histamine used to induce rhythmic behavior, and the level of activity of the endogenous nitrovasodilator, EDRF. While both superficially influenced the form of the oscillations, it follows that neither are key control variables involved in their genesis. Nonlinear analysis of data obtained in the presence of NG-nitro-L-arginine methyl ester (L-NAME), which blocks EDRF synthesis, provided insights into the intrinsic smooth muscle control mechanisms responsible for generating rhythmic activity. The oscillations exhibited distinct "fast" and "slow" components (periods of 5-20 secs and 1-5 min. respectively). The former involved ion movements at the cell membrane and was inhibited by low [Ca2+]o, verapamil (which blocks voltage-dependent Ca2+ influx) and tetraethylammonium (which blocks Ca(2+)-activated outward K+ channels), whereas the latter involved Ca(2+)-induced Ca2+ release from intracellular stores and was inhibited by ryanodine. All such interventions decreased the overall fractal dimension of the responses to a value < 2, thus removing one degree of complexity (and hence control variable) from the dynamics. We conclude that the nonlinear interaction between a fast membrane oscillator and a slow intracellular oscillator generates chaos in vascular smooth muscle and that exogenous constrictor agonists and EDRF may be regarded as permissive and modulatory influences, respectively.
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PMID:Mechanisms underlying chaotic vasomotion in isolated resistance arteries: roles of calcium and EDRF. 818

This study tests the hypothesis that halothane-induced inhibition of the endothelium-derived relaxing factor/nitric oxide (EDRF/NO) pathway significantly contributes to cardiovascular performance and thus reduces the vasoconstrictor response to NO synthesis inhibitors in vivo. We determined the effects of the administration of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in chronically instrumented, halothane-anesthetized sheep and in awake control animals. Six sheep underwent halothane anesthesia (1.5 vol%) with mechanical ventilation. Five sheep were studied in the awake state with spontaneous breathing. Both groups received a bolus of L-NAME (25 mg/kg), followed 4 h later by L-arginine (300 mg/kg) to reverse the effects of L-NAME. L-NAME administration caused a significant increase in pulmonary and systemic vascular resistance (P < 0.05) in both groups. However, L-NAME produced a sharp increase in mean arterial and pulmonary artery pressures only in the control group, whereas the pressor response in the halothane group was attenuated. Cardiac output, which was significantly lower after L-NAME administration in both groups, increased after L-arginine. The results suggest that halothane does not significantly alter the EDRF/NO-mediated effects on the vasculature but potentiates the cardiac depressant effect of L-NAME.
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PMID:Effects of halothane anesthesia on vasoconstrictor response to NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis, in sheep. 825 Mar 15

By using non-linear techniques to analyse irregular histamine-induced pressure oscillations in an isolated rabbit ear resistance artery, we have shown that the pressure oscillations are generated by deterministic rather than stochastic mechanisms. The average fractal dimension of the oscillations was between 2 and 3, thus implying that three (or more) independent control variables were necessary to account for the complexity of the dynamics. EDRF suppressed the pressure oscillations, but their fractal dimension was not altered by graded stimulation of EDRF activity by acetylcholine, or by inhibition of EDRF activity with NG-nitro-L-arginine methyl ester (L-NAME) or haemoglobin. This implies that EDRF is not one of the primary control variables involved in the genesis of their dynamics. The oscillations exhibited distinct 'fast' and 'slow' components, with periods of 5-20 s and 1-5 min respectively. The fast subsystem involved ion movements at the cell membrane level, and was inhibited by low [Ca2+]o, by verapamil (which inhibits voltage-dependent Ca2+ influx) and by tetraethylammonium (TEA) and apamin (which block Ca(2+)-activated outward K+ channels). In contrast, the slow subsystem was selectively inhibited by ryanodine, and therefore involved intracellular Ca(2+)-induced Ca2+ release. Each of these interventions decreased the fractal dimension to < 2 and thus removed one degree of freedom from the dynamics. We conclude that the interaction of a fast membrane oscillator and a slow intracellular oscillator generates chaotic pressure oscillations which are modulated by EDRF.
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PMID:Modulation of chaotic pressure oscillations in isolated resistance arteries by EDRF. 829 81

1. The aims of this study were to compare in the rat isolated perfused lung preparation, the dilator actions of nicorandil, pinacidil and nitroglycerin on the hypoxic pulmonary pressure response with or without hypercapnic acidosis and to investigate the possible involvement of K channels and EDRF in these effects. 2. Isolated lungs from male Wistar rats (260-320 g) were ventilated with 21%O2 + 5%CO2 + 74%N2 (normoxia) or 5%CO2 + 95%N2 (hypoxia) and perfused with a salt solution supplemented with ficoll and gassed with 40%CO2 + 60%N2 to produce hypercapnic acidosis. Glibenclamide (1 microM), charybdotoxin (0.1 microM), NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) and methylene blue (30 microM) were used to block KATP channels, KCa channels, EDRF synthesis and guanylate cyclase, respectively. 3. Hypoxic pressure response was significantly increased by hypercapnic acidosis (+115%, P < 0.001), L-NAME (+111%, P < 0.001), methylene blue (+100%, P < 0.05) but not by glibenclamide or charybdotoxin. In contrast none of these inhibitors affected the hypoxic hypercapnic acidosis response. 4. Nicorandil, pinacidil and nitroglycerin caused relaxation during the hypoxic pressure response and hypoxic hypercapnic acidosis response. Nicorandil was more potent in the latter. Glibenclamide inhibited the relaxant effects of nicorandil and pinacidil but not those of nitroglycerin during hypoxia alone. In contrast, glibenclamide inhibited the relaxant effects of the three drugs during hypoxia + hypercapnia. Charybdotoxin inhibited the relaxant effect of pinacidil during normocapnia and hypoxia but not those of nicorandil or nitroglycerin. Methylene blue inhibited partially the dilator response to pinacidil but did not modify the effects of nitroglycerin or nicorandil. 5. It is concluded that in the rat isolated lung preparation, EDRF limits hypoxic pulmonary vasoconstriction but not hypoxic vasoconstriction potentiated by hypercapnic acidosis, whereas KATP or KCa channels are not involved in either case. Nicorandil and pinacidil dilate pulmonary vessels mainly through KATP channels but the effects of pinacidil may also involve an additional mechanism of action through KCa channels. Finally it is suggested that nitroglycerin may partly exert its relaxant effects through KATP channels.
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PMID:Comparison of the effects of nicorandil, pinacidil and nitroglycerin on hypoxic and hypercapnic pulmonary vasoconstriction in the isolated perfused lung of rat. 864 7

In addition to stretch, some hormones and neurotransmitters influence atrial natriuretic factor (ANF) secretion from the mammalian heart. In the present study, we investigated the effect of specific inhibition of nitric oxide/endothelium-derived relaxing factor (NO/ EDRF) on release of ANF from the isolated spontaneously beating heart during basal conditions and in response to arginine vasopressin (AVP; 3 x 10(-8) M), acetylcholine (ACh; 10(-6) M), and angiotensin II (ANG II; 4 x 10(-7) M) to determine whether NO is involved as a mediator of basal and hormone-modulated secretion of ANF. Basal secretion from control hearts remained stable for the duration of the experiment. Intracoronary perfusion of the heart with AVP, ACh, and ANG II reduced ANF secretion significantly by 58 +/- 4, 51 +/- 6, and 26 +/- 8%, respectively, independently of concomitant changes in coronary flow and heart rate. The NO donor sodium nitroprusside (SNP, 10(-4) M) inhibited ANF secretion comparably to AVP and ACh. The effect of SNP was not affected by inhibition of NO synthase activity with NG-nitro-L-arginine methyl ester (L-NAME; 3 x 10(-5) M). Similarly, L-arginine, (3 x 10(-4) M) but not its stereoisomer D-arginine (3 x 10(-4) M), significantly reduced ANF secretion. Subsequent perfusion with AVP singly or in combination with L-arginine or D-arginine did not affect ANF secretion further. The inhibitor of NO synthase NG-monomethyl-L-arginine (L-NMMA, 3 x 10(-5) M) did not affect basal secretion, but prevented the inhibitory effect of AVP and ACh. The effect of ANG II was not changed by L-NMMA. These results indicate that AVP and ACh inhibit ANF secretion in the isolated heart indirectly by stimulating NO/EDRF and suggest a novel function of NO/EDRF as a negative modulator of ANF secretion.
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PMID:Effect of nitric oxide inhibition on secretion of atrial natriuretic factor in isolated rat heart. 876 65

1. The aims of this study were to compare in the rat isolated perfused lung preparation, the antagonist effects of iloprost, a stable analogue of prostacyclin, and prostaglandin E1 (PGE1) on the hypoxic pulmonary pressure response, and to investigate the possible involvement of KATP and KCa channels and of EDRF (NO) in the effects. In addition, iloprost and PGE1 effects were compared to those of adenosine and forskolin. 2. Isolated lungs from male Wistar rats (260-320 g) were ventilated with 21% O2 + 5% CO2 + 74% N2 (normoxia) or 5% CO2 + 95% N2 (hypoxia) and perfused with a salt solution supplemented with ficoll. Glibenclamide (1 microM), charybdotoxin (0.1 microM), NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) were used to block KATP, KCa channels and NO synthesis, respectively. 3. Iloprost, PGE1, adenosine and forskolin caused relaxation during the hypoxic pressure response. The order of potency was: iloprost > PGE1 = forskolin > adenosine. EC50 values were 1.91 +/- 0.52 10(-9) M, 3.31 +/- 0.58 10(-7) M, 3.24 +/- 0.78 10(-7) M and 7.70 +/- 1.68 10(-5) M, respectively. Glibenclamide, charybdotoxin and L-NAME inhibited partially the relaxant effects of iloprost and forskolin but not those of PGE1. 4. It is concluded that in the rat isolated lung preparation, iloprost and forskolin but not PGE1 dilate pulmonary vessels partly through KATP channels, KCa and nitric oxide release. Furthermore our results suggest that the role of cycli AMP in these effects is not unequivocal.
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PMID:Role of potassium channels and nitric oxide in the effects of iloprost and prostaglandin E1 on hypoxic vasoconstriction in the isolated perfused lung of the rat. 903 43

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