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)

The goal of this study was to determine the role of the synthesis and release of nitric oxide in modulating alterations in microvascular permeability of the hamster cheek pouch in response to adenosine 5'-diphosphate and bradykinin. We used intra-vital fluorescent microscopy to examine the permeability of the hamster cheek pouch to agonists before and following application of enzymatic inhibitors of nitric oxide, NG-monomethyl-L-arginine (L-NMMA; 0.01, 0.1, and 1.0 microM) and NW-nitro-L-arginine methyl ester (L-NAME; 0.01, 0.1, and 1.0 microM). Increases in permeability of the hamster cheek pouch were quantitated by the formation of microvascular leaky sites. ADP and bradykinin produced an increase in the number of venular leaky sites, and superfusion of L-NMMA and L-NAME significantly decreased ADP- and bradykinin-induced increases in microvascular permeability. To determine the specificity of nitric oxide blockade on microvascular permeability, we examined changes in permeability in response to adenosine, and examined the effects of D-NMMA on microvascular permeability. Adenosine-induced increases in permeability were not altered by treatment with L-NMMA, and D-NMMA did not inhibit ADP-induced increases in microvascular permeability. Thus, these findings suggest that production of nitric oxide, in response to application of ADP and bradykinin, has a role in modulating macromolecular permeability of the hamster cheek pouch in vivo.
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PMID:Role of nitric oxide in modulating permeability of hamster cheek pouch in response to adenosine 5'-diphosphate and bradykinin. 152 62

1. The receptors mediating the vasodilator responses to adenosine in the isolated mesenteric arterial bed of the rat were identified by use of selective agonists and antagonists and the involvement of the endothelium was examined. 2. Adenosine-mediated dilatation of the mesentery was potentiated by the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM), but in contrast, removal of the endothelium substantially reduced the responses to adenosine. 3. The order of potency of adenosine receptor agonists was: 5'-N-ethylcarboxamidoadenosine (NECA) > 2-p-(-2-carboxyethyl)phenethylamino-5'-N-ethylcarboxamidoadenosine (CGS 21680) > 2-chloro-N6-cyclopentyl-adenosine (CCPA) > or = adenosine, suggesting the presence of A2A receptors. 4. Adenosine-mediated dilatation was inhibited by the non-selective adenosine receptor antagonist, 8-phenyltheophylline (3 microM) and by the A2A receptor antagonist 8-(3-chlorostyryl)caffeine (500 nM), but was unaffected by the A1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX; 10 nM). 5. Reducing the pH of the perfusate to 6.8 potentiated the actions of both CGS 21680 and adenosine, but the vasodilator effects of carbachol were the same at both pH values. The adenosine response at the lower pH as at pH 7.4, was unaffected by DPCPX. The actions of the nitrovasodilator, sodium nitroprusside, were also potentiated at pH 6.8 relative to those at the higher pH value but smaller responses were obtained at the lower pH value with forskolin, a stimulator of adenylyl cyclase, than at pH 7.4. 6. It is concluded that the adenosine receptor mediating dilatation of the rat mesenteric arterial bed is of the A2A subtype, that the response, under the conditions used, is apparently partly dependent on the endothelium (but not due to the release of nitric oxide), and that the response to activation of this receptor is potentiated by a reduction in pH which is similar to that seen in ischaemic conditions.
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PMID:Effects of pH on responses to adenosine, CGS 21680, carbachol and nitroprusside in the isolated perfused superior mesenteric arterial bed of the rat. 859 Sep 83

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

We investigated the effect of inhibitors of endothelium-derived nitric oxide and sodium-potassium (Na(+)-K+) pumps on adenosine receptor-mediated hyperpolarization of porcine coronary artery smooth muscle with and without endothelium. The average resting membrane potential (RMP) in porcine coronary artery smooth muscle was -51.5 +/- 0.2 and -50.7 +/- 0.2 mV, in the presence and absence of endothelium, respectively. Neither ouabain, N-nitro-L-arginine methyl ester (L-NAME) nor ouabain and L-NAME in combination significantly affected the resting membrane potential in the absence of vasodilator agonists. Adenosine agonists, 2-chloroadenosine and 5'-N-ethylcarboxamidoadenosine at 10(-5) M caused a significant increase in RMP with intact endothelium and caused a smaller but significant increase in RMP in the absence of endothelium. Ouabain (10(-5) M) in the absence of L-NAME significantly reduced hyperpolarization due to 2-chloroadenosine and 5'-N-ethylcarboxamidoadenosine in the presence of endothelium. However, in the absence of endothelium, its inhibitory effect was not significant. When ouabain plus L-NAME (10(-5) M) were given simultaneously, the hyperpolarization caused by adenosine agonists was significantly further attenuated nearly to the RMP level. Attenuation of the response to 2-chloroadenosine and 5'-N-ethylcarboxamidoadenosine by ouabain was not reversed by the nitric oxide precursor, L-arginine (10(-5) M) both in the presence and absence of endothelium. These results suggest that hyperpolarization of vascular smooth muscle of the porcine coronary artery by adenosine agonists is at least partly endothelium dependent and possibly involves the Na(+)-K+ pump and the release of nitric oxide.
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PMID:Effect of ouabain on adenosine receptor-mediated hyperpolarization in porcine coronary artery smooth muscle. 909 86

Our objective was to determine the vasodilator effect of adenosine and isoproterenol on the hepatic artery (HA) and superior mesenteric artery (SMA) before and after blockade of nitric oxide (NO) production to evaluate the possibility of organ specificity. Vascular circuits supplied blood flow to the liver or intestine in cats under pentobarbital sodium anesthesia. The NO synthase (NOS) antagonist N(G)-nitro-L-arginine methyl ester (L-NAME; 2.5 mg/kg iv) increased arterial pressure from 106.4 +/- 7.6 to 141.4 +/- 8.1 mmHg and raised basal vascular tone in the SMA but not in the HA. The NOS substrate L-arginine (75 mg/kg) reversed these effects. The decrease in perfusion pressure in response to adenosine was 51.7 +/- 2.9, 135.2 +/- 6.1, and 16.7 +/- 2.4 mmHg, respectively, for control and after L-NAME and L-arginine. Isoproterenol was also potentiated in the SMA. Adenosine and isoproterenol were not potentiated in the HA by L-NAME. Potentiation did not occur when HA or SMA basal tone was elevated by norepinephrine. In conclusion, L-NAME increased basal tone for the SMA and potentiated the dilation induced by adenosine and isoproterenol in the SMA but not in the HA. This study provides evidence that there is a highly organ-specific compensatory mechanism in which the absence of NO promotes potentiation of other vasodilators.
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PMID:Potentiation to vasodilators by nitric oxide synthase blockade in superior mesenteric but not hepatic artery. 912 71

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 ionic mechanisms underlying the negative dromotropic effect of adenosine were studied in calcium-tolerant myocytes isolated from the region of the rabbit atrioventricular (AV) node. Action potentials and membrane currents were recorded by using the whole cell patch clamp technique. Adenosine (1 to 50 microM) abolished the spontaneous activity of AV node myocytes with hyperpolarization of the membrane potential. Voltage clamp experiments showed that adenosine induced an inwardly rectifying, time-independent potassium current. These effects were antagonized by 8-cyclopentyl-1,3-dipropylxanthine and produced by ribose 5-phosphate isomerase A, indicating that they were mediated by the A1 adenosine receptor. Adenosine also had a small direct inhibitory action on the inward calcium current (ICa) but had a more marked indirect action following stimulation of the calcium current by isoprenaline. The isoprenaline-induced increase in ICa was abolished in the presence of adenosine 10 microM. In cells pretreated with the nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME), the isoprenaline-induced increase in ICa was not reduced by the addition of adenosine. Coincubation of the cells with L-NAME plus L-arginine (the endogenous substrate of nitric oxide synthase) restored the adenosine-induced attenuation of ICa. A membrane permeable analogue of cGMP, 8Br cGMP, an inhibitor of cGMP-stimulated phosphodiesterase, prevented the antiadrenergic effect of adenosine. These results suggest that adenosine activates guanylyl cyclase following the production of nitric oxide, and the subsequent stimulation of phosphodiesterase enhances the breakdown of isoprenaline-elevated cAMP leading to a reduction in the stimulated ICa. In conclusion, the important ionic mechanisms of the actions of adenosine on AV nodal cells are a direct effect, with activation of a potassium conductance and an indirect antiadrenergic effect on ICa, which is mediated by nitric oxide production and phosphodiesterase stimulation.
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PMID:Ionic mechanisms of the effect of adenosine on single rabbit atrioventricular node myocytes. 944

1. Sympathetic vasoconstriction is attenuated by metabolic events in contracting rat skeletal muscle, in part by activation of ATP-sensitive potassium (KATP) channels. However, the specific metabolites in contracting muscle that open KATP channels are not known. We therefore asked if contraction-induced attenuation of sympathetic vasoconstriction is mediated by the endogenous vasodilators nitric oxide (NO), adenosine, or prostaglandins PGI2 or PGF2, all of which are putative KATP channel openers. 2. In anaesthetized rats, hindlimb contraction alone significantly attenuated the vasoconstrictor responses to lumbar sympathetic nerve stimulation. Inhibition of NO synthase with N-nitro-L-arginine methyl ester (L-NAME, 5 mg kg-1, i.v.) partially reversed this effect of contraction, resulting in enhanced sympathetic vasoconstriction in contracting hindlimb. Subsequent treatment with the KATP channel blocker glibenclamide (20 mg kg-1, i.v.) had no further effect on sympathetic vasoconstriction in contracting hindlimb. 3. This effect of L-NAME to partially reverse contraction-induced attenuation of sympathetic vasoconstriction was not replicated by D-NAME (5 mg kg-1, i.v.) or angiotensin II (12.5 ng kg-1 min-1, i.v.), the latter used as a hypertensive control. 4. Adenosine receptor blockade with 8-(p-sulphophenyl)theophylline (10 mg kg-1, i.v.) or cyclooxygenase inhibition with indomethacin (5 mg kg-1, i.v.) had no effect on contraction-induced attenuation of sympathetic vasoconstriction. 5. These results suggest that NO plays an important role in the precise regulation of blood flow in exercising skeletal muscles by opposing sympathetic vasoconstriction. Although the underlying mechanism is not known, it may involve NO-induced activation of vascular KATP channels.
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PMID:Nitric oxide mediates contraction-induced attenuation of sympathetic vasoconstriction in rat skeletal muscle. 950 40

Recently, it has been demonstrated that the endothelium of corpus cavernosum (CC) plays an important role on smooth muscle relaxation, which is crucial to initiate and maintain erection. We investigated the effect of long-lasting additional testosterone propionate (TP) therapy on endothelium-dependent and -independent relaxations of isolated rabbit CC. Isolated CC strips were mounted in organ baths and isometric tension was recorded. Addition of a specific inhibitor of nitric oxide synthesis, NG-nitro-L-arginin methyl ester (L-NAME), into the organ bath had no effect on the relaxation responses to adenosine (ADO), adenosine 5'-triphosphate (ATP) and sodium nitroprusside (SNP) in isolated CC strips precontracted with phenylepherine, but completely inhibited relaxation responses produced by ADP. Adenosine and adenine nucleotides relaxed the phenylepherine-induced contractile response in control strips with the potency order: ADO (62.8 +/- 3.2%) > ATP (37.1 +/- 5.2%) > ADP (25.8 +/- 2.5%). The relaxation responses to ADO, ATP and SNP in isolated rabbit CC strips were not significantly altered by additional TP therapy. The relaxation responses produced by ADP were significantly enhanced following 1 and 2 months TP therapy as compared with controls. However, in the group treated with TP for 2 months followed by a 2 months drug-free period, relaxation responses were significantly reduced compared to 1 and 2 months treatment groups, and approached control values. Increased relaxation responses to ADP following 1 and 2 months additional TP therapy may be a result of increased endothelial purinergic receptor density, or it may be due to stimulation and/or release of endothelial nitric oxide (NO) by TP.
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PMID:Effect of additional testosterone on purinergic responses in isolated rabbit corpus cavernosum strips. 960 72

Renal hemodynamic changes could play a key role in radiocontrast media-induced nephropathy (RCIN), although the pathophysiological mechanisms are unclear. We investigated the role of adenosine in RCIN caused by sodium diatrizoate (Urografin, 3 ml/kg) in nitro-L-Arg methyl ester (L-NAME)-hypertensive rats in different hydration states [eight weeks of L-NAME (50 mg/liter) in drinking water; high or low sodium intake for the last two weeks]. In clearance experiments under thiobutabarbital anesthesia in these previously mentioned animals, glomerular filtration rate (GFR), renal blood flow (RBF), and mean arterial pressure (MAP) were measured in the presence or absence of the adenosine A1-receptor antagonist 8-cyclopropyl-1,3-dipropylxanthine (DPCPX, 100 microg/kg bolus plus 10 microg/kg/hr). DPCPX or pretreatment did not change control hemodynamics. Contrast medium caused GFR and RBF to fall significantly in volume-depleted rats (from 0.29 +/- 0.02 to 0.21 +/- 0.02 ml/min/100 g and 5.4 +/- 0.3 to 4.0 +/- 0.4 ml/min, respectively) without change in MAP. In volume-expanded rats, changes were not significant (0.25 +/- 0.01 to 0.24 +/- 0.02 ml/min/100 g and 5.6 +/- 0.3 to 5.3 +/- 0.4 ml/min, respectively). In the volume-depleted rats, changes were prevented by DPCPX (0.27 +/- 0.02 to 0.24 +/- 0.02 ml/min/100 g and 4.8 +/- 0.1 to 5.0 +/- 0.1 ml/min, respectively). The acute hemodynamic effects elicited by contrast medium in L-NAME hypertensive rats thus can be prevented by volume expansion. Adenosine, via A1-receptors, contributes to the adverse effects of contrast media.
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PMID:Adenosine and extracellular volume in radiocontrast media-induced nephropathy. 973 87

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