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

1. The direct vascular effects of adenosine and ATP were compared in the isolated and perfused mesenteric arterial bed of the rat. The actions of analogues of adenosine and ATP were also examined. 2. In preparations at basal tone, adenosine lacked vasoconstrictor actions, while ATP elicited dose-dependent vasoconstrictor responses. When the tone of preparations was raised by adding methoxamine to the perfusate, adenosine and its stable analogue, 2-chloroadenosine (2-CADO) elicited dose-dependent vasodilation. The A2 adenosine receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA) was active at lower doses than adenosine, while the A2a-selective agonist, CGS 21680 and the selective A1 agonist, N6-cyclopentyladenosine (CPA) failed to induce vasodilatation. ATP and its analogue, 2-methylthio ATP, elicited dose-dependent vasodilatation at doses 400 fold lower than adenosine. 3. Vasodilator responses to adenosine and 2-CADO were sensitive to antagonism by 1 microM 8-sulphophenyltheophylline (8-SPT) and were unaffected by inhibition of nitric oxide synthase by N omega-nitro-L-arginine methyl ester (L-NAME). In contrast, vasodilator responses to ATP were not sensitive to antagonism by 8-SPT and were almost abolished by L-NAME treatment. 4. These results indicate that in the rat mesenteric arterial bed, while both adenosine and ATP participate in the purinergic control of vascular tone, adenosine appears to be a weaker vasodilator than ATP and lacks vasoconstrictor action. A2b adenosine receptors account for the adenosine-induced vasodilatation which is independent of the production of nitric oxide.
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PMID:Contribution of P1-(A2b subtype) and P2-purinoceptors to the control of vascular tone in the rat isolated mesenteric arterial bed. 758 85

We studied the effects of adenosine (AD) and its analogues, 5'-N-ethylcarboxamidoadenosine (NECA) and 2-chloroadenosine (CAD) on membrane potential of porcine coronary artery with an without endothelium, conducting experiments with addition of indomethacin (10(-5) M) to rule out involvement of prostanoids. Average resting membrane potential (RMP) in porcine coronary artery was -51.1 +/- 0.2 and -50.3 +/- 0.2 mV, with and without endothelium, respectively. AD agonists at 10(-5) M caused a significant increase in RMP to -69.5 +/- 0.2 mV for AD, to -82.2 +/- 0.3 mV for CAD, and to -81.2 +/- 0.3 mV for NECA in porcine coronary arteries with intact endothelium. Moreover, AD agonists at 10(-5) M caused a smaller but significant increase in RMP to -54.3 +/- 0.2 mV for AD, -56.1 +/- 0.1 mV for CAD, and -61.1 +/- 0.2 mV for NECA without endothelium. The average RMP for human coronary artery with and without endothelium was -66.1 +/- 0.5 and -64.0 +/- 0.4, respectively. Qualitatively, similar effects of AD and its analogues were observed in two human coronary arteries. The AD receptor antagonist, 8-sulfophenyltheophylline (8-SPT, 10(-5) M) blocked hyperpolarization caused by AD and its analogues with and without endothelium both in porcine and human coronary arteries. The hyperpolarization caused by CAD and NECA in porcine coronary artery was attenuated in part by the nitric oxide (NO) synthase inhibitors N-monomethyl-L-arginine (L-NMMA, 10(-5) M) and N-nitro-L-arginine methylester (L-NAME, 10(-5) M), and the effect of L-NAME was reversed by L-arginine (L-ARG, 10(-4) M).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of endothelium in hyperpolarization of coronary smooth muscle by adenosine and its analogues. 775 49

In this study, we tested the hypothesis that nitric oxide (NO) and adenosine (ADO) are the principal mediators of severe hypoxia-induced vasodilation. In addition, we examined whether activation of N-methyl-D-aspartate (NMDA) receptors and/or perivascular nerves plays a role. A closed cranial window and intravital microscopy system was used to monitor diameter changes in pial arterioles (approximately 40 microns) in anesthetized rats. The relative contributions of ADO, NMDA, NO, and neuronal activation to hypoxic cerebrovasodilation were assessed using the blockers 8-sulfophenyltheophylline (8-SPT), MK-801, nitro-L-arginine methylester (L-NAME), and tetrodotoxin (TTX). Two experimental series were studied. In the first, we tested the effects of NOS inhibition, via topical L-NAME (1 mM), on moderate (PaO2 approximately 46 mmHg) then severe (PaO2 approximately 34 mmHg) hypoxia-induced dilation. To confirm that L-NAME was affecting specifically NO-dependent responses, we also examined, in each experiment, the vasodilatory responses to topical applications of NOS-dependent (adenosine diphosphate (ADP); acetylcholine (ACh)) and -independent (sodium nitroprusside (SNP)) agents, in the presence of L-NAME or, in controls, the presence of D-NAME or no added analogue. In the second series, topical suffusions of ADP, ADO, and NMDA were sequentially applied, followed by 5 min exposure to severe hypoxia (PaO2 approximately 32 mmHg). Following return to normoxia, a suffusion of either 8-SPT (10 microM), MK-801 (10 microM), TTX (1 microM), or 8-SPT+MK-801 was initiated (or, in controls, application of a drug-free suffusate was maintained), and the above sequence repeated. In control, TTX, and 8-SPT+MK-801 experiments, baseline conditions were then restored and hypercapnia (PaCO2 = 70-85 mmHg) was imposed. In the series 1 control groups, moderate and severe hypoxia elicited approximately 20% and 35-40% increases in diameter, respectively. L-NAME attenuated ADP- and ACh-induced dilations, did not alter the arteriolar responses to SNP or moderate hypoxia, but prevented further dilation upon imposition of severe hypoxia. This suggested that 45-50% of the severe hypoxia response was NO-dependent. In series 2, 8-SPT blocked the adenosine response and reduced severe hypoxia-induced dilation by 46%. MK-801 predictably blocked NMDA-induced relaxation and reduced the hypoxic response by 42%. When combined, 8-SPT and MK-801 affected hypoxic vasodilation additively. After TTX, the ADP and ADO responses were normal, but NMDA and hypoxia responses were completely blocked. Hypercapnia-induced dilation was unaffected by TTX or 8-SPT+MK-801. The results imply that severe hypoxia-induced release of NO and ADO, and the accompanying pial arteriolar dilation, are wholly dependent on the capacity to generate action potentials in perivascular nerves. The similarity of the L-NAME and MK-801 effects on hypoxic cerebrovasodilation suggests that the NO-dependency, to a large degree, derives from NMDA receptor activation.
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PMID:Role of nitric oxide, adenosine, N-methyl-D-aspartate receptors, and neuronal activation in hypoxia-induced pial arteriolar dilation in rats. 875 Sep 62

1. The presence of A2 receptors mediating relaxation in the rat isolated aorta has been previously demonstrated. However, agonist dependency of the degree of rightward shift elicited by 8-sulphophenyltheophylline (8-SPT) led to the suggestion that the population of receptors in this tissue is not a homogeneous one. In this study we have re-examined the effects of 8-SPT in the absence and presence of the NO synthase inhibitor L-NAME (NG-nitro-L-arginine methyl ester) and investigated antagonism of responses by the potent A2a receptor ligands PD 115,199 (N-[2-dimethylamino)ethyl]-N-methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3 dipropyl-1H-purin-8-yl)) benzene sulphonamidexanthine), ZM 241385 (4-(2-[7-amino-2-(2-furyl) [1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-yl amino]ethyl)phenol), and CGS 21680 (2-[p-(2-carboxyethyl)phenylamino]-5'-N-ethylcarboxamidoadenosine). We have also investigated the antagonist effects of BWA1433 (1,3-dipropyl-8-(4-acrylate)phenylxanthine) which has been shown to have affinity at rat A3 receptors. 2. Adenosine, R-PIA (N6-R-phenylisopropyl adenosine), CPA (N6-cyclopentyladenosine) and NECA (5'-N-ethylcarboxamidoadenosine) all elicited relaxant responses in the phenylephrine pre-contracted rat isolated aorta with the following potency order (p[A50] values in parentheses): NECA (7.07 +/- 0.11) > R-PIA (5.65 +/- 0.10) > CPA (5.05 +/- 0.12) > adenosine (4.44 +/- 0.12). 3. 8-SPT (10-100 microM) caused parallel rightward shifts of the E/[A] curves to NECA (pKB = 5.23 +/- 0.16). A smaller rightward shift of E/[A] curves to CPA was observed (pA2 = 4.85 +/- 0.17). However, no significant shifts of E/[A] curves to either adenosine or R-PIA were observed. 4. In the absence of endothelium E/[A] curves to NECA and CPA were right-shifted compared to controls. However, removal of the endothelium did not produce a substantial shift of adenosine E/[A] curves, and E/[A] curves to R-PIA were unaffected by removal of the endothelium. 5. In the presence of L-NAME (100 microM) E/[A] curves to NECA and CPA were right-shifted. However, no further shift of the CPA E/[A] curve was obtained when 8-SPT (50 microM) was administered concomitantly. The locations of curves to R-PIA and adenosine were unaffected by L-NAME (100 microM). 6. In the presence of PD 115,199 (0.1 microM) a parallel rightward shift of NECA E/[A] curves was observed (pA2 = 7.50 +/- 0.19). PD 115,199 (0.1 and 1 microM) gave smaller rightward shifts of E/[A] curves to R-PIA and CPA, but E/[A] curves to adenosine were not significantly shifted in the presence of PD 115,199 (0.1 or 1 microM). 7. The presence of ZM 241385 (3 nM-0.3 microM) caused parallel rightwad shifts of NECA E/[A] curves (pKB = 8.73 +/- 0.11). No significant shifts of E/[A] curves to adenosine, CPA or R-PIA were observed in the presence of 0.1 microM ZM 241385. 8. CGS 21680 (1 microM) elicited a relaxant response equivalent to approximately 40% of the NECA maximum response. In the presence of this concentration of CGS 21680, E/[A] curves to NECA were right-shifted in excess of 2-log units, whereas E/[A] curves to R-PIA were not significantly shifted. 9. BWA1433 (100 microM) caused a small but significant right-shift of the E/[A] curve to R-PIA yielding a pA2 estimate of 4.1 IB-MECA (N6-(3-iodo-benzyl)adenosine-5(1)-N-methyl uronamide) elicited relaxant responses which were resistant to blockade by 8-SPT (p[A]50 = 5.26 +/- 0.13). 10. The results suggest that whereas relaxations to NECA (10 nM-1 microM) are mediated via adenosine A2a receptors, which are located at least in part on the endothelium, R-PIA and CPA may activate A2b receptors on the endothelium and an additional, as yet undefined site, which is likely to be located on the smooth muscle and which is not susceptible to blockade by 8-SPT, PD 115,199 or ZM 241385. This site is unlikely to be an A3 receptor since the very small shift obtained in the presence of BWA1433 (100 microM), and the low potency of IB-MECA is not consistent with the affin
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PMID:Activation of multiple sites by adenosine analogues in the rat isolated aorta. 883 79

1. In Saffan-anaesthetized rats, we have further investigated the mechanisms underlying the vasodilatation induced by adenosine in skeletal muscle by acute systemic hypoxia (breathing 8% O2 for 5 min). 2. In eleven rats the nitric oxide (NO) synthesis inhibitor nitro-L-arginine methyl ester (L-NAME, 10 mg kg-1, i.v.) reduced the increase in femoral vascular conductance (FVC) induced by hypoxia by approximately 50%. L-NAME had similar effects on the increase in FVC induced by intra-arterial (I.A.) infusion of adenosine (at 1.2 mg kg-1 min-1 for 5 min via the tail artery) and by ATP (I.A., 1 mg kg-1 min-1 for 5 min). Subsequent administration of the adenosine receptor antagonist 8-sulphophenyl theophylline (8-SPT, 20 mg kg-1, i.v.) virtually abolished the adenosine- and ATP-induced increase in FVC. 3. In a further nine rats, 8-SPT reduced the increase in FVC induced by hypoxia by approximately 50%. This remaining increase in FVC was substantially reduced by L-NAME. 4. In an additional nine rats, alpha,beta-methyleneADP (160 micrograms kg-1, i.v.) which inhibits the 5'-ectonucleotidase that degrades AMP to adenosine, reduced the peripheral vasodilatation (fall in arterial blood pressure, ABP) induced by ATP infusion, but had no effect on the increase in FVC or decrease in ABP evoked by systemic hypoxia. 5. These results provide the first evidence that the muscle vasodilatation induced by adenosine during systemic hypoxia is mainly dependent on NO synthesis. They also suggest that adenosine is released as such rather than being formed extracellularly from AMP. Given evidence that extraluminal adenosine acts in an NO-independent fashion we propose that hypoxia releases adenosine from the endothelium. Our results also indicate that hypoxia induces muscle vasodilatation that is adenosine independent but NO dependent: they allow the possibility that this is partly mediated by ATP released from the endothelium.
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PMID:Studies on the roles of ATP, adenosine and nitric oxide in mediating muscle vasodilatation induced in the rat by acute systemic hypoxia. 888 65

1. Adenosine and its analogues induced an increase in flow rate when infused into the rat isolated perfused heart. The agonist potency order obtained was 2-(rho-(2-carboxyethyl)phenethyl-amino)-5'-N-ethylcarboxamidoadenosine (CGS 21680) > or = 5'-N-ethylcarboxamidoadenosine (NECA) > N6-cyclopentyladenosine = adenosine, although the maximal response obtained for CGS 21680 was only 70% of that achieved by NECA. NG-Nitro-L-arginine methyl ester (L-NAME), the nonselective adenosine antagonist 8-rho-(sulfophenyl)theophylline (8-SPT) and the A2a selective antagonist N-[2-(dimethylamino)ethyl]-N-methyl-4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3- diprophyl-1H-purin-8-yl)benzene sulfonamide (PD 115, 119) reduced responses to the adenosine agonists, but some of this reduction was shown to be due to a nonspecific decrease in flow rate as well as a specific inhibitory action. 2. When this functional antagonism is taken into account, the results suggest that the increase in flow rate induced by the adenosine agonists was mediated by A2 receptors, with the increase in flow rate induced by CGS 21680 mediated by A2a receptors, whereas that induced by NECA was mediated by A2b receptors. 3. L-NAME did not appear to have any effect on the increase in flow rate induced by the adenosine agonists, suggesting that these responses were probably endothelium independent and do not involve the nitric oxide pathway.
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PMID:Involvement of functional antagonism in the effects of adenosine antagonists and L-NAME in the rat isolated heart. 937 50

The aim of this study was to characterise the receptor(s) mediating relaxations to adenosine and its analogues in the hamster isolated aorta. Adenosine relaxed the aorta but there was no significant difference between pIC20 values in the absence and presence of 8-sulphophenyltheophylline (8-SPT, 50 microM), although there was a small right-shift (approximately threefold) of the lower portion of the curve in the presence of 8-SPT. However, in the presence of the adenosine uptake inhibitor nitrobenzylthioinosine (NBTI, 1 microM), curves to adenosine were left-shifted by approximately 100-fold and an apparent pK(B) for 8-SPT of 5.79+/-0.05 was obtained. Likewise, 5'-N-ethylcarboxamidoadenosine (NECA) relaxed the aorta but curves were biphasic. The first phase of the curve was blocked by 8-SPT (10-100 microM, pA2 = 5.75+/-0.14) and the A2A-selective antagonist 4-(2-[7-amino-2-(2-furyl) [1,2,4]-triazolo[2,3-a][1,3,5]triazin-5-ylaminolethyl) phenol (ZM 241385, 3 nM-1 microM, pK(B)=9.17+/-0.10). Similarly, the A2A-selective agonist 2-[p)-(2-carbonylethyl)-phenylethylamino]-5'-N-ethylcarboxam idoadenosine (CGS 21680) relaxed the tissues but curves were biphasic and the first phase was again blocked by ZM 241385 (10 nM, apparent pK(B)=9.06+/-0.34). In contrast, relaxations to N6-R-phenylisopropyladenosine (R-PIA), N6-cyclopentyladenosine (CPA), 2-chloroadenosine (2-CADO) and N6-(3-iodobenzyl)-adenosine-5'-N-methyluronamide (IB-MECA) were not blocked by 8-SPT (50 microM). Responses to IB-MECA were also not blocked by the A3 receptor antagonist 3-ethyl-5-benzyl-2-methyl-6-phenyl-4-phenylethynyl-1,4-(+/-)-dihyd ropyridine-3,5-dicarboxylate (MRS 1191, 30 microM). The asymptote of the first phase of curves to NECA was markedly reduced (and in some preparations the first phase was completely abolished) both in the presence of N(G)-nitro-L-arginine methyl ester (L-NAME, 0.1 mM), and in the absence of endothelium. Likewise, the first phase of curves to CGS 21680 was abolished both in the presence of L-NAME (0.1 mM) and in the absence of endothelium. In contrast, there were only relatively small shifts to the right of curves to adenosine and the other analogues in the presence of L-NAME or the absence of endothelium (between three- and fivefold). The data suggest the presence of A2A receptors which are located on the endothelium and mediate release of nitric oxide. These receptors are activated by NECA, CGS 21680 and adenosine (in the presence of uptake blockade). The resistance to blockade of relaxations to adenosine (in the absence of uptake inhibitor), CPA, R-PIA, 2-CADO, IB-MECA and high concentrations of NECA and CGS 21680 by 8-SPT or ZM 241385 suggests the presence of an additional mechanism(s). Data obtained with adenosine in the absence and presence of NBTI suggest that the endogenous ligand may cause relaxation via an intracellular mechanism.
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PMID:Characterisation of adenosine receptors mediating relaxation in hamster isolated aorta. 1111 38

We studied the role of adenosine and P2 receptors in the pelvic nerve stimulation-induced penile tumescence in anesthetized dogs. A local intracavernous injection of adenosine induced the tumescence, which was abolished by intracavernous 8-(p-sulfophenyl)theophylline (8-SPT), an unspecific adenosine receptor antagonist, and by 4-(2-[7-amino-2-(2-furyl)[1,2,4]triazolo[2,3-a][1,3,5]triazin-5-yl amino]ethyl)phenol (ZM241385), an adenosine A(2A) receptor antagonist. ATP also induced the tumescence, which was diminished by 8-SPT, but not by reactive blue-2, a P2 receptor antagonist. Neither intracavernous beta, gamma-meATP nor ADP(beta)S, P2X and P2Y receptor agonists, induced tumescence. N(G)-nitro-L-arginine (L-NAME), a nitric oxide synthase inhibitor, and T-1032, a phosphodiesterase type V inhibitor, had no effects on the tumescence induced by adenosine. 8-SPT and reactive blue-2 had no effects on the tumescence induced by pelvic nerve stimulation. These results show that although exogenous adenosine and ATP induce tumescence, neither the adenosine nor the P2 receptor is involved in the tumescence induced by pelvic nerve stimulation in anesthetized dogs.
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PMID:Role of adenosine and P2 receptors in the penile tumescence in anesthetized dogs. 1167 74

We used two experimental models to prove that resveratrol (trans-3,4',5-trihydroxystilbene) reduces cardiac ischemic-reperfusion injury by means of a nitric oxide- and adenosine-dependent mechanism. (1). ACUTE EX VIVO: resveratrol (10 microM, 10 min) infusion in Langendorff-perfused normoxic rat hearts significantly increased adenosine release and coronary flow compared with baseline. After 30-min low-flow ischemia, vasodilation, still present at reperfusion, was completely abolished by resveratrol plus adenosine antagonist 8-(p-sulfophenyl)theophylline (SPT, 50 microM) administration. (2). CHRONIC IN VIVO: rats received tap water containing 25 mg/l resveratrol for 15 days or normal water. Twenty-four hours after, their hearts were Langendorff-perfused and submitted to 60-min low-flow ischemia and reperfusion. The resveratrol-treated hearts showed better functional recovery at reperfusion and significant vasodilation, but no variation in high-energy phosphates (31P Nuclear Magnetic Resonance). N(G)-nitro-L-arginine methyl ester (L-NAME, 30 microM), a nonselective nitric oxide synthase inhibitor, or SPT (50 microM) administered for 10 min prior to the low-flow ischemia cancelled the effects. This suggests that long-term moderate resveratrol consumption could play an important role in late cardioprotective effects.
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PMID:Resveratrol provides late-phase cardioprotection by means of a nitric oxide- and adenosine-mediated mechanism. 1265 Aug 40

In contrast to classical beta-adrenoreceptor antagonists, nebivolol and carvedilol possess endothelium-dependent vasorelaxant properties. It has been proposed that nebivolol and carvedilol activate microvascular endothelium into producing NO by the release of extracellular ATP and subsequent stimulation of endothelial P(2) receptors. Here we tested this hypothesis in the coronary circulation of the isolated guinea pig heart. We analyzed the role of NO in the coronary vasodilatation induced by nebivolol and carvedilol as well as a possible involvement of extracellular ATP in these responses. Nebivolol and carvedilol (3-30 x 10(-6) M) induced a concentration-dependent coronary vasodilatation that was inhibited by NO-synthase inhibitor, L-NAME (10(-4) M). In contrast to nebivolol and carvedilol, neither atenolol nor labetalol acted as a coronary vasodilator. Vasodilatation induced by nebivolol and carvedilol was affected neither by the P(1) receptor antagonist, 8-sulfophenyl theophylline (8-SPT, 10(-5) M), nor by the P(2) receptor antagonist, suramin (10(-5) M). On the other hand, ATP-induced coronary vasodilatation (0.3-10 x 10(-6) M) was strongly inhibited by L-NAME (10(-4) M), partially inhibited by 8-SPT (10(-5) M), while suramin (10(-5) M) had a minor effect. In conclusion, in the isolated guinea pig heart nebivolol and carvedilol, but not their classical counterparts (atenolol, labelatol), act as NO-dependent coronary vasodilators. It seems unlikely that this response is mediated by the release of extracellular ATP.
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PMID:Nebivovol and carvedilol induce NO-dependent coronary vasodilatation that is unlikely to be mediated by extracellular ATP in the isolated guinea pig heart. 1733 79


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