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

This study examined the systemic and pulmonary vasodilator effects of sodium nitroprusside (SNP) and adenosine during experimental pulmonary hypertension with and without inhibition of endogenous NO synthesis. Male New Zealand White rabbits were anesthetized and mechanically ventilated. The NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) was administered to 15 of the 28 rabbits. Pulmonary hypertension was then produced in all rabbits by U46619, a thromboxane A2 mimetic. SNP was infused in 14 rabbits (7 L-NAME, 7 control) at doses of 0.5-20 microg/kg/min; adenosine was infused in the other 14 rabbits (8 L- NAME, 6 control) at doses of 12.5-300 microg/kg/min. The U46619 dose required to produce pulmonary hypertension was significantly lower in the L-NAME group. SNP dose-dependently decreased pulmonary (Ppa) and systemic (Psa) artery pressures and systemic vascular resistance (SVR). Both Ppa and Psa were decreased more with SNP in the L-NAME than in the no L-NAME group. The SNP ED50 for the decrease in PVR was almost threefold lower in the L-NAME group. Adenosine dose-dependently decreased Ppa, Psa, PVR and SVR. The adenosine ED50 for the decreases in PVR and SVR were similar in the L-NAME group and the control group. We conclude that inhibition of endogenous NO synthesis shifts the dose-response curves for both the pulmonary and systemic vasodilator effects to the left for the nitrovasodilator SNP but not for the non-nitrovasodilator adenosine.
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PMID:Inhibition of endogenous nitric oxide synthesis potentiates the effects of sodium nitroprusside but not of adenosine in experimental pulmonary hypertension. 983 29

Adenosine (Ado) plays an important role in regulation of coronary vascular tone with nitric oxide (NO) and ATP-sensitive K(+) (K(+)(ATP)) channels. In vitro, it was reported that subendocardial (Endo) arterioles are more sensitive to Ado than subepicardial (Epi) arterioles. The purpose of this study was to observe enhanced vasodilation of Endo arterioles directly and to evaluate possible roles of K(+)(ATP) channels and NO in the different responses of Endo and Epi arterioles to Ado-induced vasodilation. We evaluated dilation of Endo and Epi arterioles (<120 micrometer) of beating canine hearts (n = 19) by Ado (20 and 50 microgram. kg(-1). min(-1) ic) before and after K(+)(ATP) channel blockade (glibenclamide; 200 microgram/kg ic), inhibition of NO synthase [N(G)-nitro-L-arginine methyl ester (L-NAME); 30 microgram. kg(-1). min(-1), 20 min ic], or glibenclamide + L-NAME using a novel needle-probe CCD intravital microscope. Ado induced dose-dependent vasodilation in both Epi and Endo arterioles, but vasodilation was greater in Endo arterioles, i.e., increase at 120 s (maximum dilation) after Ado (50 microgram. kg(-1). min(-1)) was 17% in Endo and 13% in Epi arterioles (P < 0.01). Endo arteriole dilation was attenuated by blockade of K(+)(ATP) channels from 18% (Ado) to 9% (Ado+glibenclamide) increase (P < 0.001) and by inhibition of NO synthase from 17% (Ado) to 9% (Ado+L-NAME) (P < 0.005). Epi arteriole vasodilation was attenuated by blockade of K(+)(ATP) channels from 15 to 9% (P < 0.005) and inhibition of NO from 16 to 10% (P < 0.005). Suppression of vascular response was additive (Endo, 14 to -1%; Epi, 12 to 3%) with glibenclamide + L-NAME. We conclude that 1) the degree of Ado-induced vasodilation was greater in Endo than in Epi arterioles, with higher sensitivity of smaller arterioles in both layers and 2) transmural difference of arteriolar sensitivity to adenosine was abolished or reversed by K(+)(ATP) channel blockade and/or by NO synthase inhibition, indicating crucial involvement of K(+)(ATP) and NO in transmural sensitivity difference.
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PMID:Role of NO and K(+)(ATP) channels in adenosine-induced vasodilation on in vivo canine subendocardial arterioles. 1056 49

The present study was aimed at investigating the effects of diabetes on the cavernosal smooth muscle relaxations mediated by adenosine and adenosine triphosphate (ATP) in tissues obtained from men and rats. Adenosine- and ATP-induced relaxant responses showed an enhanced sensitivity with an unaltered effectiveness in diabetic men. Adenosine-elicited relaxation in diabetic rat corporeal tissues exhibited enhanced effectiveness with unaltered sensitivity, whereas ATP-induced relaxations were decreased in diabetic animals when compared to control animals. Tetraethylammonium pretreatment, but not glibenclamide, L-NAME and 8-phenyltheophylline, normalized enhanced apparent affinity to adenosine in tissue from diabetic men and effectiveness (E(max)) to adenosine in diabetic rats. These results suggest that adenosine-elicited relaxation in diabetes is controlled at the receptor level events including K(+) channels in men whereas in rats postreceptor-related events including K(+) channels control the adenosine-induced relaxation. These relaxations to adenosine and ATP in men and rats with and without diabetes may be nitric oxide-independent mechanisms. Our results also suggest that ATP-induced relaxation did not involve K(ATP) channels and Ca-activated K(+) channels.
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PMID:Altered relaxant responses to adenosine and adenosine 5'-triphosphate in the corpus cavernosum from men and rats with diabetes. 1065 60

Adenosine transport was characterized in human umbilical artery smooth muscle cells isolated from non-diabetic and diabetic pregnant subjects. Transport of adenosine was mediated by a Na+-independent transport system inhibited by nanomolar concentrations of nitrobenzylthioinosine (NBMPR) in both cell types. Diabetes increased adenosine transport, an effect that was associated with a higher maximal velocity (Vmax) for NBMPR-sensitive (es) saturable nucleoside transport (18 +/- 2 vs. 61 +/- 3 pmol (microgram protein)-1 min-1, P < 0.05) and the maximal number of binding sites (Bmax) for specific [3H]NBMPR binding (74 +/- 4 vs. 156 +/- 10 pmol (microgram protein)-1, P < 0.05), with no significant changes in the Michaelis-Menten (Km) and dissociation (Kd) constants, respectively. Adenosine transport was unaltered by inhibition of nitric oxide (NO) synthase (with 100 microM NG-nitro-L-arginine methyl ester, L-NAME) or protein synthesis (with 1 microM cycloheximide), but was increased by inhibition of adenylyl cyclase activity (with 100 microM, SQ-22536) in non-diabetic cells. Diabetes-induced adenosine transport was blocked by L-NAME and associated with an increase in L-[3H]citrulline formation from L-[3H]arginine and intracellular cGMP, but with a decrease in intracellular cAMP compared with non-diabetic cells. Expression of inducible NO synthase (iNOS) was unaltered by diabetes. Dibutyryl cGMP (dbcGMP) increased, but dibutyryl cAMP (dbcAMP) decreased, adenosine transport in non-diabetic cells. dbcGMP or the NO donor S-nitrosoacetylpenicillamine (SNAP, 100 microM) did not alter the diabetes-elevated adenosine transport. However, activation of adenylyl cyclase with forskolin (1 microM), directly or after incubation of cells with dbcAMP, inhibited adenosine transport in both cell types. Our findings provide the first evidence that adenosine transport in human umbilical artery smooth muscle cells is mediated by the NBMPR-sensitive transport system es, and that its activity is upregulated by gestational diabetes.
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PMID:Nitric oxide, cGMP and cAMP modulate nitrobenzylthioinosine-sensitive adenosine transport in human umbilical artery smooth muscle cells from subjects with gestational diabetes. 1091 79

We investigated the hypothesis that the purine nucleotide ATP and its nucleoside adenosine cause pulmonary vasodilation in fetal lambs by the release of nitric oxide (NO). We also investigated the potential role of K(+)(ATP) channels in mediating the effects of ATP and adenosine on NO. We surgically prepared 28 fetal lambs to measure pulmonary and systemic pressures and pulmonary flow. We investigated the effects of glibenclamide and pinacidil (inhibitor and agonist, respectively, for K(+)(ATP) channels), N-nitro-L-arginine (N-LA) and its methyl ester, N-nitro-L-arginine methyl ester (L-NAME) (inhibitors of endothelium-derived NO synthesis), and U46619 (a thromboxane mimetic) on pulmonary vasodilation caused by adenosine and ATP. Adenosine decreased the pulmonary artery pressure and pulmonary vascular resistance (PVR) at doses of 0.08-2.5 microM/kg/min and increased the left pulmonary flow at doses of 0.3-2.5 microM/kg/min in control experiments. N-LA, L-NAME and glibenclamide attenuated the effects of adenosine at doses of < 2.5 microM/ kg/min and pinacidil potentiated its effects. ATP decreased the pulmonary artery pressure and PVR and increased the pulmonary flow at doses of 0.15-2.5 microM/kg/min in control experiments. N-LA and L-NAME attenuated the effects of ATP at doses of < 2.5 microM/kg/min, whereas glibenclamide and pinacidil had no effect on the response to ATP. U46619 increased the basal pulmonary vascular tone, but did not significantly alter the vasodilative responses to ATP and adenosine. In conclusion, adenosine and ATP cause NO-dependent pulmonary vasodilation in fetal lambs. The activation of K(+)(ATP) channels plays a role in adenosine-induced pulmonary vasodilation. The mechanism by which ATP causes NO release and pulmonary vasodilation requires further investigation.
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PMID:Adenosine and ATP cause nitric oxide-dependent pulmonary vasodilation in fetal lambs. 1104 72

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

The effects of elevated D-glucose on adenosine transport were investigated in human cultured umbilical vein endothelial cells isolated from normal pregnancies. Elevated D-glucose resulted in a time- (8-12 h) and concentration-dependent (half-maximal at 10+/-2 mM) inhibition of adenosine transport, which was associated with a reduction in the Vmax for nitrobenzylthioinosine (NBMPR)-sensitive (es) saturable nucleoside with no significant change in Km. d-Fructose (25 mM), 2-deoxy-D-glucose (25 mM) or D-mannitol (20 mM) had no effect on adenosine transport. Adenosine transport was inhibited following incubation of cells with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA; 100 nM, 30 min to 24 h). D-Glucose-induced inhibition of transport was abolished by calphostin C (100 nM, an inhibitor of PKC), and was not further reduced by PMA. Increased PKC activity in the membrane (particulate) fraction of endothelial cells exposed to D-glucose or PMA was blocked by calphostin C but was unaffected by NG-nitro-L-arginine methyl ester (L-NAME; 100 microM, an inhibitor of nitric oxide synthase (NOS)) or PD-98059 (10 microM, an inhibitor of mitogen-activated protein kinase kinase 1). D-Glucose and PMA increased endothelial NOS (eNOS) activity, which was prevented by calphostin C or omission of extracellular Ca2+ and unaffected by PD-98059. Adenosine transport was inhibited by S-nitroso-N-acetyl-l, d-penicillamine (SNAP; 100 microM, an NO donor) but was increased in cells incubated with L-NAME. The effect of SNAP on adenosine transport was abolished by PD-98059. Phosphorylation of mitogen-activated protein kinases p44mapk (ERK1) and p42mapk (ERK2) was increased in endothelial cells exposed to elevated D-glucose (25 mM for 30 min to 24 h) and the NO donor SNAP (100 microM, 30 min). The effect of D-glucose was blocked by PD-98059 or L-NAME, which also prevented the inhibition of adenosine transport mediated by elevated D-glucose. Our findings provide evidence that D-glucose inhibits adenosine transport in human fetal endothelial cells by a mechanism that involves activation of PKC, leading to increased NO levels and p42-p44mapk phosphorylation. Thus, the biological actions of adenosine appear to be altered under conditions of sustained hyperglycaemia.
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PMID:Regulation of adenosine transport by D-glucose in human fetal endothelial cells: involvement of nitric oxide, protein kinase C and mitogen-activated protein kinase. 1111 5

1. We have developed a model to study the inhibitory properties of endogenous autacoids triggered by systemically-administered vasoactive peptides, on platelet aggregation ex vivo in the mouse. 2. Adenosine diphosphate (ADP) (0.5-10 microM) induces a concentration-dependent aggregation of platelet-rich plasma derived from C57BL/6 mice. Intravenously-administered endothelin-1 (0.01-1 nmolx kg(-1)), the selective ETB agonist, IRL-1620 (0.0 -1 nmol x kg(-1)) or bradykinin ( 1-100 nmol x kg(-1)) significantly reduced in a dose-dependent fashion the ADP-induced platelet aggregation. 3. The non-selective cyclo-oxygenase (COX) inhibitor, indomethacin, a selective COX-2 inhibitor NS-398 or the prostacyclin synthase inhibitor, tranylcypromine (10 mg x kg(-1)), markedly reduced the inhibitory properties of endothelin-1, whereas only a combination of both indomethacin, NS-398 or tranylcypromine and L-NAME (10 mg x kg(-1)) were required to abolish the response to bradykinin. 4. An ETB-selective antagonist (BQ-788) or knockout of the B2 receptor gene (in B2 knockout mice) abolishes the platelet inhibitory properties of endothelin-1 and bradykinin, respectively. 5. Our results suggest that intravenously-administered endothelin-1 and bradykinin, through ETB and B2 receptor activation, respectively, inhibit platelet aggregation ex vivo in the mouse. The inhibitory properties of endothelin-1 require the activation of COX-2 and the subsequent generation of prostacyclin. In addition to the two previously mentioned factors, nitric oxide is required for the anti-aggregatory effects of bradykinin.
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PMID:Role of ETB and B2 receptors in the ex vivo platelet inhibitory properties of endothelin and bradykinin in the mouse. 1118 35

In the isolated Agama lizard aorta, acetylcholine (ACh; 3 nM-100 microM), noradrenaline (NA; 30 nM-0.3 mM), adrenaline (Adr; 30 nM-300 microM), adenosine 5'-triphosphate (ATP; 30 nM-1 mM), alpha,beta-methylene ATP (alpha,beta-meATP; 10 nM-10 microM), beta,gamma-methylene ATP (beta,gamma-meATP; 0.1-300 microM), 2-methylthio ATP (2-meSATP; 30 nM-30 microM) and high concentrations of uridine triphosphate (UTP; 1 microM-1 mM), all produced constriction. The P2 receptor antagonists pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS; 30 microM), suramin (0.1 mM) and Reactive blue 2 (30 microM) all raised vascular tone and could not be utilized and the antagonist 2'-O-(trinitrophenyl) ATP (TNP-ATP; 0.1 microM) had no effect on responses to the ATP analogues. alpha,beta-MeATP (3 microMx3) desensitised responses to alpha,beta-meATP (10 microM) and beta,gamma-meATP (0.3 mM), but not to ATP (0.3 mM) or 2-meSATP (30 microM). On pre-constricted aorta (EC50 concentration of either ACh or Adr), adenosine (1 microM-1 mM), the A1-selective agonist N6-cyclopentyl adenosine (CPA; 1-300 microM) [but not the A2- and A3-selective agonists CGS 21680 and IB-MECA respectively (both up to 30 microM)] and sodium nitroprusside (10 nM-100 microM) produced vasodilatation. Adenosine vasodilatation was antagonised by 8-p-sulfophenyl-theophylline (8-pSPT; 30 microM) but not by N(omega)-nitro-L-arginine methyl ester (L-NAME; 0.1 mM). ATP (up to 0.3 mM), 2-meSATP (up to 10 microM) and UTP (up to 1 mM) were not vasodilators. In summary, A1 receptors mediating relaxation and excitatory P2X1 receptors were identified in the smooth muscle of the lizard aorta. However, in contrast to mammalian aorta, P2Y receptors on endothelial cells mediating vasodilatation via nitric oxide do not appear to be present.
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PMID:Identification of P1 and P2 purinoceptors in the aorta of the lizard (Agama sp.). 1125 14

The Na(+)-Ca(2+) exchanger is a protein present in the cell membrane of many cell types. In heart it plays important roles in Ca homeostasis and ionic current generation. Recently, it has been reported that the beta-adrenergic agonist isoprenaline (ISO) can increase directly Na(+)-Ca(2+) exchanger activity in guinea-pig ventricular myocytes. Adenosine (ADO) exerts anti-adrenergic properties that make it effective against some arrhythmias and the aim of the present study was to determine whether or not ADO can antagonize the direct modulatory effect of ISO on the exchanger.Whole-cell patch clamp measurements of Na(+)-Ca(2+) exchanger current (I(NaCa)) were made from guinea-pig ventricular myocytes, with major interfering currents inhibited. I(NaCa) was measured at 378 degrees C as current sensitive to external nickel (Ni(2+), 10 mM) during an applied descending voltage ramp. ISO (1 microM) significantly increased both inward and outward I(NaCa). This effect was abolished in the presence of ADO (200 microM). ADO alone did not significantly alter the amplitude of I(NaCa). The effect of ADO on the response of I(NaCa) to ISO was mimicked by the A(1)ADO receptor agonist N(6)-cyclopentyladenosine (CPA, 10 microM), whereas the effect of ADO on the response of I(NaCa) to ISO was inhibited by the A(1)ADO receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, 2 microM). These data suggest that the A(1)ADO receptor mediated the response. The anti-adrenergic effects on I(NaCa) of ADO were not affected by the protein kinase C (PKC) inhibitor, chelerythrine (CLT, 1 microM), nor by the nitric oxide (NO) synthase inhibitor, N (G)-nitro-L-arginine methyl ester((L)-NAME, 0.5 mM). Moreover, in the presence of PKC activator phorbol 12-myristate 13-acetate (PMA, 1 microM) or exogenous NO donor sodium nitroprusside (SNP, 100 microM), ISO preserved its stimulatory effect on I(NaCa). However, prior incubation of myocytes with pertussis toxin (PTX, 5 microg ml(-1) did prevent the effect of ADO. The anti-adrenergic effect of ADO on I(NaCa) was mimicked by externally applied carbachol (CCh, 10 microM), a muscarinic receptor agonist. We conclude that ADO antagonized the effect of beta-adrenergic stimulation of I(NaCa) by directly activating inhibitory G-protein (G(i))-linked A(1) receptors in guinea-pig ventricular myocytes. These findings may suggest a novel mechanism by which adenosine exerts some of its antiarrhythmic effects.
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PMID:Anti-adrenergic effect of adenosine on Na(+)-Ca(2+) exchange current recorded from guinea-pig ventricular myocytes. 1129 91


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