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 present experiments in mice were performed to determine the steady-state effects of exogenous adenosine on the vascular resistance of the whole kidney, of superficial blood vessels, and of afferent arterioles. The steady-state effect of an intravenous infusion of adenosine (5, 10, and 20 microg/min) in wild-type mice was vasodilatation as evidenced by significant reductions of renal and superficial vascular resistance. Resistance decreases were augmented in adenosine 1 receptor (A1AR) -/- mice. Renal vasodilatation by the A2aAR agonist CGS 21680A [2-p-(2-carboxyethyl)phenethyl-amino-5'-N-ethylcarboxamido-adenosine hydrochloride] (0.25, 0.5, and 1 microg/kg/min) and inhibition of adenosine-induced relaxation by the A2aAR antagonist 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] (20 mg/kg) suggests that the reduction of renovascular resistance was largely mediated by A2aAR. After treatment with Nomega-nitro-L-arginine methyl ester (L-NAME) adenosine was unable to alter superficial blood flow and resistance significantly indicating that adenosine-induced dilatation is NO-dependent. Absence of a dilatory effect in endothelial nitric-oxide synthase (NOS) -/- mice suggests endothelial NOS as the source of NO. When infused into the subcapsular interstitium, adenosine reduced superficial blood flow through A1AR activation. Adenosine (10(-7) M) constricted isolated perfused afferent arterioles when added to the bath but not when added to the luminal perfusate. Luminal adenosine caused vasoconstriction in the presence of L-NAME or the A2AR antagonist 3,7-dimethyl-1-(2-propynyl)xanthine. Our data show that global elevation of renal adenosine causes steady-state vasorelaxation resulting from adenosine 2 receptor (A2AR)-mediated generation of NO. In contrast, selective augmentation of adenosine around afferent arterioles causes persistent vasoconstriction, indicating A1AR dominance. Thus, adenosine is a renal constrictor only when it can interact with afferent arteriolar A1AR without affecting the bulk of renal A2AR at the same time.
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PMID:Vasoconstrictor and vasodilator effects of adenosine in the mouse kidney due to preferential activation of A1 or A2 adenosine receptors. 1612 Aug 12

Nitric oxide (NO) is a physiological mediator of skeletal muscle function. Specifically, NO affects cellular respiration and muscle contractility; however, the reduced blood flow and convective O2 delivery that result from impaired vasodilatation when NO synthase (NOS) is inhibited in vivo have obscured past interpretations of the effects of NO. Therefore, we studied the effect of NOS inhibition in an in situ pump-perfused rat hindlimb to test the hypothesis that NOS inhibition would improve contractile and aerobic metabolic performance. Pump perfusion permitted matching of convective O2 delivery (516 +/- 16 micromol O2 min(-1) (100 g)(-1); mean +/- s.e.m.) between groups, allowing us to investigate the effects of NOS inhibition independent of this variable. Three groups were studied. The perfusate of one group was treated with both adenosine (0.01 mm) and the NOS inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME; 1 mm). Adenosine is a vasodilator that can act through both NO-dependent and -independent pathways; the NO-independent vasodilatory action of adenosine allowed us to match the perfusion rate and convective O2 delivery in this L-NAME group to those of the other groups. In the second group the perfusate was treated with adenosine only (Ado). In the third group the perfusate received no treatment and served as a control (Con). Oxygen consumption (VO2) was on average 26 and 14% lower during the contraction bout in L-NAME and Ado, respectively, versus Con. In Ado, lactate efflux was similar to Con and force was reduced in proportion to versus Con, whereas L-NAME was associated with a 32% lower lactate efflux and similar force to Con. Therefore, the lower :force development ratio in the L-NAME group demonstrates that the O2 cost of force development is reduced by NOS inhibition independent of convective O2 delivery.
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PMID:Nitric oxide synthase inhibition reduces the O2 cost of force development in rat hindlimb muscles pump perfused at matched convective O2 delivery. 1612 49

The aims of the study were to examine the roles of the ATP-sensitive potassium (K(ATP)) channel, the endothelium, and nitric oxide (NO) in the responses of rat coronary small arteries to adenosine and hypoxia. Segments of rat coronary vessel were investigated in vitro using pressure myography; all vessels studied developed stable spontaneous myogenic tone during equilibration. Glibenclamide (a K(ATP) channel inhibitor) reversed pinacidil but not 2-deoxyglucose-induced dilation. Both adenosine and hypoxia dilated the vessels, and glibenclamide did not reverse these responses. Endothelial removal or N(G)-nitro-L-arginine methyl ester (L-NAME) inhibited the dilation to adenosine by approximately 50%; subsequent addition of glibenclamide was without effect. Hypoxic dilation was completely inhibited by endothelium removal or L-NAME. We conclude that adenosine- and hypoxia-induced dilation of rat coronary arteries does not appear to involve the K(ATP) channel. Adenosine-induced dilation is partially and hypoxic dilation is completely dependent on endothelium-derived NO.
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PMID:Adenosine and hypoxic dilation of rat coronary small arteries: roles of the ATP-sensitive potassium channel, endothelium, and nitric oxide. 1624 19

Human umbilical vein endothelial cells (HUVEC) from gestational diabetes exhibit reduced adenosine uptake and increased nitric oxide (NO) synthesis. Adenosine transport via human equilibrative nucleoside transporters 1 (hENT1) is reduced by NO by unknown mechanisms in HUVEC. We examined whether gestational diabetes-reduced adenosine transport results from lower hENT1 gene (SLC29A1) expression. HUVEC from gestational diabetes exhibit reduced SLC29A1 promoter activity when transfected with pGL3-hENT1(-2154) compared with pGL3-hENT1(-1114) constructs, an effect blocked by N(G)-nitro-L-arginine methyl ester (L-NAME, NOS inhibitor), but unaltered by S-nitroso-N-acetyl-L,D-penicillamine (SNAP, NO donor). In cells from gestational diabetes transfected with pGL3-hENT1(-2154), L-NAME increased, but SNAP did not alter promoter activity and hENT1 expression. However, in cells from normal pregnancies L-NAME increased, but SNAP reduced promoter activity and hENT1 expression. Adenovirus-silenced eNOS expression increased hENT1 expression and activity in cells from normal or gestational diabetic pregnancies. Thus, reduced adenosine transport may result from downregulation of SLC29A1 expression by NO in HUVEC from gestational diabetes. These findings explain the accumulation of extracellular adenosine detected in cultures of HUVEC from gestational diabetes. In addition, fetal endothelial dysfunction could be involved in the abnormal fetal development and growth seen in gestational diabetes.
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PMID:Nitric oxide reduces adenosine transporter ENT1 gene (SLC29A1) promoter activity in human fetal endothelium from gestational diabetes. 1668 63

The aims of the present study were firstly, to characterize pharmacologically the subtypes of P(1) purinoreceptors involved in the inhibitory effects induced by exogenous adenosine in longitudinal smooth muscle of mouse colon, and secondly, to examine differences in the function and distribution of these receptors between proximal and distal colon. Adenosine (100 microM-3 mM) caused a concentration-dependent reduction of the amplitude of spontaneous contractions in the proximal colon, and muscular relaxation in the distal colon. In the proximal colon, adenosine effects were antagonized by a selective A(1) receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine (DPCPX, 10 nM), but were not modified by 3,7-dimethyl-1-propargylxanthine (DMPX, 10 microM) or by 9-chloro-2-(2-furanyl)-5-((phenylacetyl)amino)- [1,2,4]triazolo[1,5-c]quinazoline (MRS 1220, 0.1 microM), selective A(2) and A(3) receptor antagonists, respectively. In the distal colon, adenosine effects were antagonized by DPCPX, DMPX, and by a selective A(2B) receptor antagonist, 8-[4-[((4-cyanophenyl)carbamoylmethyl)oxy]phenyl]-1,3-di(n-propyl) xanthine (MRS 1754, 10 microM), but not by 8-(3-chlorostyryl)-caffeine (CSC, 10 microM), a selective A(2A) receptor antagonist, or by MRS 1220. Tetrodotoxin (TTX 1 microM), the nitric oxide (NO) synthase inhibitor, N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM), or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10 microM), an inhibitor of soluble guanylyl cyclase, reduced adenosine effects only in distal colon. In addition, L-NAME induced a further reduction of adenosine relaxation in the presence of DPCPX, but not in the presence of MRS 1754. From these results we conclude that, in the murine proximal colon, adenosine induces inhibitory effects via TTX-insensitive activation of A(1) receptor. In the distal colon, adenosine activates both A(1) and A(2B) receptors, the latter located on enteric inhibitory neurons releasing NO.
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PMID:Inhibitory responses to exogenous adenosine in murine proximal and distal colon. 1684 44

L-Arginine transport and nitric oxide (NO) synthesis (L-arginine/NO pathway) are stimulated by insulin, adenosine or elevated extracellular D-glucose in human umbilical vein endothelial cells (HUVEC). Adenosine uptake via the human equilibrative nucleoside transporters 1 (hENT1) and 2 (hENT2) has been proposed as a mechanism regulating adenosine plasma concentration, and therefore its vascular effects in human umbilical veins. Thus, altered expression and/or activity of hENT1 or hENT2 could lead to abnormal physiological plasma adenosine level. We have characterized insulin effect on adenosine transport in HUVEC cultured in normal (5 mM) or high (25 mM) D-glucose. Insulin (1 nM) increased overall adenosine transport associated with higher hENT2-, but lower hENT1-mediated transport in normal D-glucose. Insulin increased hENT2 protein abundance in normal or high D-glucose, but reduced hENT1 protein abundance in normal D-glucose. Insulin did not alter the reduced hENT1 protein abundance, but blocked the reduced hENT1 and hENT2 mRNA expression induced by high D-glucose. Insulin effect on hENT1 mRNA expression in normal D-glucose was blocked by N(G)-nitro-L-arginine methyl ester (L-NAME, NO synthase inhibitor) and mimicked by S-nitroso-N-acetyl-L,D-penicillamine (SNAP, NO donor). L-NAME did not block insulin effect on hENT2 expression. In conclusion, insulin stimulation of overall adenosine transport results from increased hENT2 expression and activity via a NO-independent mechanism. These findings could be important in hyperglycemia-associated pathological pregnancies, such as gestational diabetes, where plasma adenosine removal by the endothelium is reduced, a condition that could alter the blood flow from the placenta to the fetus affecting fetus growth and development.
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PMID:Insulin restores glucose inhibition of adenosine transport by increasing the expression and activity of the equilibrative nucleoside transporter 2 in human umbilical vein endothelium. 1692 60

Cutaneous vasoconstrictor responsiveness may be impaired by substance(s) directly or indirectly responsible for cutaneous active vasodilatation. In this study, we tested the hypothesis that endogenous nitric oxide (NO) attenuates the reduction in cutaneous vascular conductance (CVC) during an orthostatic challenge combined with whole-body heating, as well as during whole-body cooling. In protocol 1, healthy subjects were pretreated with an intradermal injection of botulinum toxin A (BTX) to block the release of neurotransmitters from nerves responsible for cutaneous active vasodilatation. On the experimental day, a microdialysis probe was placed at the BTX-treated site as well as at two adjacent untreated sites. NG-nitro-l-arginine methyl ester (L-NAME, 10 mm) was perfused through the probe placed at the BTX-treated site and at one untreated site. After confirmation of the absence of cutaneous vasodilatation at the BTX site during whole-body heating, adenosine was infused through the microdialysis probe at this site to increase skin blood flow to a level similar to that at the untreated site. Subsequently, 30 and 40 mmHg lower-body negative pressures (LBNPs) were applied. The reduction in CVC to LBNP was greatest at the BTX-treated site (15.0 +/- 2.4% of the maximum level (% max)), followed by the L-NAME-treated site (11.3 +/- 2.6% max), and then the untreated site (3.8 +/- 3.0% max; P < 0.05 for all comparisons). In protocol 2, two microdialysis membranes were inserted in the dermal space of one forearm. Adenosine alone was infused at one site while the other site received adenosine and L-NAME. The reduction in CVC in response to whole-body cooling was significantly greater at the L-NAME-treated site than at the adjacent adenosine alone site. These results suggest that endogenous NO is capable of attenuating cutaneous vasoconstrictor responsiveness.
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PMID:Endogenous nitric oxide attenuates neutrally mediated cutaneous vasoconstriction. 1794 10

We previously demonstrated a role for voltage-dependent K(+) (K(V)) channels in coronary vasodilation elicited by myocardial metabolism and exogenous H(2)O(2), as responses were attenuated by the K(V) channel blocker 4-aminopyridine (4-AP). Here we tested the hypothesis that K(V) channels participate in coronary reactive hyperemia and examined the role of K(V) channels in responses to nitric oxide (NO) and adenosine, two putative mediators. Reactive hyperemia (30-s occlusion) was measured in open-chest dogs before and during 4-AP treatment [intracoronary (ic), plasma concentration 0.3 mM]. 4-AP reduced baseline flow 34 +/- 5% and inhibited hyperemic volume 32 +/- 5%. Administration of 8-phenyltheophylline (8-PT; 0.3 mM ic or 5 mg/kg iv) or N(G)-nitro-L-arginine methyl ester (L-NAME; 1 mg/min ic) inhibited early and late portions of hyperemic flow, supporting roles for adenosine and NO. 4-AP further inhibited hyperemia in the presence of 8-PT or L-NAME. Adenosine-induced blood flow responses were attenuated by 4-AP (52 +/- 6% block at 9 microg/min). Dilation of arterioles to adenosine was attenuated by 0.3 mM 4-AP and 1 microM correolide, a selective K(V)1 antagonist (76 +/- 7% and 47 +/- 2% block, respectively, at 1 microM). Dilation in response to sodium nitroprusside, an NO donor, was attenuated by 4-AP in vivo (41 +/- 6% block at 10 microg/min) and by correolide in vitro (29 +/- 4% block at 1 microM). K(V) current in smooth muscle cells was inhibited by 4-AP (IC(50) 1.1 +/- 0.1 mM) and virtually eliminated by correolide. Expression of mRNA for K(V)1 family members was detected in coronary arteries. Our data indicate that K(V) channels play an important role in regulating resting coronary blood flow, determining duration of reactive hyperemia, and mediating adenosine- and NO-induced vasodilation.
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PMID:Voltage-dependent K+ channels regulate the duration of reactive hyperemia in the canine coronary circulation. 1837 17

The present study was performed to examine the involvement of nitric oxide (NO) signaling pathway in the anti-convulsant effect of adenosine against pentylenetetrazol seizure threshold in mice. Minimal dose of pentylenetetrazol (i.v., mg/kg) needed to induce different phases (myoclonic jerks, generalized clonus and tonic extension) of convulsions was recorded as an index of seizure threshold. Adenosine (100 or 200 mg/kg i.p.) produced a significant increase in the seizure threshold for convulsions induced by pentylenetetrazol i.v. infusion. The anti-convulsant effect of adenosine (100 mg/kg i.p.) was prevented by either L-arginine (50 mg/kg i.p.) [substrate for nitric oxide synthase (NOS)] or sodium nitroprusside (3 mg/kg i.p.) [a NO donor]. On the other hand, N(G)-nitro-L-arginine methyl ester (L-NAME, 2.5 mg/kg i.p.) [a non-selective NOS inhibitor] or 7-nitroindazole (7-NI) (25 mg/kg i.p.) [a specific neuronal nitric oxide synthase (nNOS) inhibitor] potentiated the anti-convulsant action of sub-effective dose of adenosine (50 mg/kg i.p.). Aminoguanidine (100 mg/kg i.p.) [a specific inducible NOS (iNOS) inhibitor] pre-treatment was not effective in inducing anti-convulsant effect with sub-effective dose of adenosine (50 mg/kg i.p.). Furthermore, the increase in seizure threshold elicited by adenosine (100 mg/kg i.p.) was also inhibited by concomitant administration with sildenafil (5 mg/kg i.p.) [phosphodiesterase 5 inhibitor]. In contrast, treatment of mice with methylene blue (1 mg/kg i.p.) [a direct inhibitor of both nitric oxide synthase (NOS) and soluble guanylate cyclase (sGC)] failed to induce anti-convulsant action with adenosine (50 mg/kg i.p.) against pentylenetetrazol i.v. infusion. The results demonstrated that the anti-convulsant action of adenosine in the pentylenetetrazol i.v. seizure threshold paradigm may possibly involve an interaction with the L-arginine-NO-cGMP pathway which may be secondary to the activation of adenosine receptors.
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PMID:Nitric oxide signaling pathway in the anti-convulsant effect of adenosine against pentylenetetrazol-induced seizure threshold in mice. 1845 33

NADPH oxidases (NOX) are the major source of reactive oxygen species (ROS) in the vasculature and contribute to the control of renal perfusion. The role of NOX2 in the regulation of blood pressure and afferent arteriole responsiveness was investigated in NOX2(-/-) and wild-type mice. Arteriole constrictions to ANG II (10(-14)-10(-6) mol/l) were weaker in NOX2(-/-) compared with wild types. N(omega)-nitro-l-arginine methyl ester (l-NAME; 10(-4) mol/l) treatment reduced basal diameters significantly more in NOX2(-/-) (-18%) than in wild types (-6%) and augmented ANG II responses. Adenosine (10(-11)-10(-4) mol/l) constricted arterioles of wild types but not of NOX2(-/-). However, simultaneous inhibition of adenosine type-2 receptors induced vasoconstriction, which was stronger in NOX2(-/-). Adenosine (10(-8) mol/l) enhanced the ANG II response in wild type, but not in NOX2(-/-). This sensitizing effect by adenosine was abolished by apocynin. Chronic ANG II pretreatment (14 days) did not change the ANG II responses in NOX2(-/-), but strengthened the response in wild types. ANG II pretreatment augmented the l-NAME response in NOX2(-/-) (-33%), but not in wild types. Simultaneous application of l-NAME and ANG II caused a stronger constriction in the NOX2(-/-) (-64%) than in wild types (-46%). Basal blood pressures were similar in both genotypes, however, chronic ANG II infusion elevated blood pressure to a greater extent in wild-type (15 +/- 1%) than in NOX2(-/-) (8 +/- 1%) mice. In conclusion, NOX2 plays an important role in the control of afferent arteriole tone and is involved in the contractile responses to ANG II and/or adenosine. NOX2 can be activated by elevated ANG II and may play an important role in ANG II-induced hypertension. NOX2-derived ROS scavenges nitric oxide, causing subsequent nitric oxide-deficiency.
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PMID:Role of NOX2 in the regulation of afferent arteriole responsiveness. 1898 86

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