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. Vascular contractions induced by K(+)-free solution and relaxation responses following the return of K+ to the organ bath were studied in mesenteric arterial rings from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with particular focus on the role of vascular adrenergic nerve-endings and endothelium. 2. In endothelium-denuded rings the omission of K+ from the incubation medium resulted in gradual contractions, the rate of which was slower in SHR than WKY. Nifedipine (1 microM) inhibited the contractions more effectively in SHR than WKY. 3. Adrenergic denervation in vitro with 6-hydroxydopamine reduced the contractions induced by the K(+)-free medium in endothelium-denuded rings. The remaining contractions after denervation were markedly greater in SHR than WKY. 4. The presence of intact vascular endothelium attenuated the K(+)-free contractions in both strains, the attenuation being smaller in SHR than WKY. NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM) and methylene blue (10 microM), but not indomethacin (10 microM), abolished the attenuating effect of endothelium on the K(+)-free contractions. L-Arginine (1 mM) reversed the effect of L-NAME in WKY but not in SHR. 5. The re-addition of K+ after full K(+)-free contractions dose-dependently relaxed the rings. The rate of this K(+)-induced relaxation was significantly slower in SHR than WKY at all K+ concentrations (0.1-5.9 mM) studied, whether the endothelium or functioning adrenergic nerve-endings were present or not. Ouabain (1 mM) totally inhibited the K+ relaxation in SHR but only partially in WKY.6. Vascular smooth muscle contractions induced by high concentrations of potassium were comparable between the strains. The EC50 for noradrenaline-induced contractions was lower in SHR than WKY, but the maximal forces did not differ significantly.7. In conclusion, the contractile response in K+-free solution more clearly differentiates vascular rings from SHR and WKY than the responses induced by the classical contractile agents noradrenaline and high concentrations of potassium. The depressant effect of the presence of intact endothelium on the K+-free contractions, which was smaller in SHR than WKY, is mediated via the endothelium-derived relaxing factor. Neurotransmitter release from vascular adrenergic nerve-endings participates less in the K+-free contractile response in SHR than WKY. Moreover, the contractile response is more dependent on calcium entry through nifedipine-sensitive calcium channels in SHR than WKY. The greater K+-free contractions of denervated endothelium-denuded rings and the reduced K+ relaxation rate in SHR when compared to WKY suggest increased cell membrane permeability and decreased activity of vascular Na+, K+-ATPase, respectively, in this type of genetic hypertension.
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PMID:Contractions induced by potassium-free solution and potassium relaxation in vascular smooth muscle of hypertensive and normotensive rats. 150 24

The possible endothelial factors involved in endothelium-dependent relaxations induced by acetylcholine (ACh) in aorta, mesenteric and femoral arteries of rabbit were analyzed. In thoracic aorta precontracted with noradrenaline, NG-nitro-L-arginine methyl ester (L-NAME) and methylene blue (MB), inhibitors of nitric oxide (NO) synthase and guanylate cyclase, practically abolished ACh relaxation. This relaxation was reduced by the Na+ pump inhibition with ouabain and K(+)-free solution, and by the blockade of Ca(2+)-dependent K+ channels with tetraethylammonium (TEA). Ouabain reduced the relaxation produced by the NO donor, sodium nitroprusside (SNP). In the mesenteric artery, L-NAME and MB produced a small reduction of ACh relaxation. However, ouabain, K(+)-free medium and TEA markedly decreased this relaxation. SNP induced a relaxation which was diminished by ouabain. In segments precontracted with high K+, ACh relaxation was abolished by L-NAME and MB. In femoral arteries, L-NAME and MB reduced ACh relaxation. The stimulated cGMP concentrations caused by ACh or SNP were less in the aorta than in mesenteric and femoral arteries. These results suggest that ACh relaxation is mediated: in aorta by endothelial NO which may hyperpolarize to some extent the smooth muscle cells through the sodium pump activation, in mesenteric artery by endothelium-derived hyperpolarizing factor and NO, the latter being clearly expressed in segments contracted with high K+, and in femoral artery essentially by endothelial NO release.
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PMID:Heterogeneity of endothelium-dependent mechanisms in different rabbit arteries. 757 2

Studies were designed to determine the extent of the involvement of endothelium-derived relaxing factor(s) other than nitric oxide (NO) in vascular relaxation in response to acetylcholine (ACh) in the rabbit renal artery. ACh (10(-9)-10(-6) M) induced concentration-dependent relaxation of isolated endothelium-intact arterial rings preconstricted with noradrenaline. NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthase, partly inhibited the ACh-induced endothelium-dependent relaxation, whereas it almost completely abolished the production of cyclic-3', 5'-guanosine monophosphate (cGMP) in these rings in response to ACh. Methylene blue, an inhibitor of guanylate cyclase, had an essentially similar effect to L-NAME on the relaxation. Indomethacin, an inhibitor of cyclooxygenase, had no effect. High concentrations of potassium chloride (to inhibit endothelium-dependent hyperpolarization), tetraethylammonium (TEA) or 4-aminopyridine (4-AP), a voltage-dependent or Ca(2+)-dependent K+ channel blocker, partly inhibited the relaxation while, in contrast, glibenclamide, an ATP-sensitive K+ channel blocker, had no effect. Ouabain, an inhibitor of Na+, K(+)-ATPase, also partly inhibited the ACh-induced relaxation, especially the higher concentration effect. Application of L-NAME together with ouabain, TEA, or a high concentration of potassium chloride completely abolished the relaxation. These results suggest that ACh-induced endothelium-dependent relaxation in the rabbit renal artery is mediated by NO, and by an other factor(s), which relaxes the vascular smooth muscle through opening K+ channels other than ATP-sensitive ones, and/or through the activation of a Na+, K(+)-pump.
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PMID:NG-nitro-L-arginine-resistant endothelium-dependent relaxation induced by acetylcholine in the rabbit renal artery. 804 Dec 28

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

1. We have previously demonstrated that adenosine-5'-O-(2-thiodiphosphate) (ADPbetaS), a potent P2Y-purinoceptor agonist, relaxed pancreatic vasculature not only through prostacyclin (PGI2) and nitric oxide (NO) release from the endothelium but also through other mechanism(s). In this study, we investigated the effects of an inhibitor of the Na+/K+ pump, of ATP-sensitive K+ (K(ATP)) channels and of small (SK(Ca)) or large (BK(Ca)) conductance Ca2+-activated K+ channels. Experiments were performed at basal tone and during the inhibition of NO synthase and cyclo-oxygenase. 2. In control conditions, ADPbetaS (15 microM) induced an initial transient vasoconstriction followed by a progressive and sustained vasodilatation. In the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME, 200 microM) the transient vasoconstriction was reversed into a one minute vasodilator effect, which was then followed by a progressive and sustained vasodilatation similar to that observed with ADPbetaS alone. The addition of indomethacin (10 microM) did not significantly modify the profile of ADPbetaS-induced vasodilatation. 3. Ouabain (100 microM) decreased basal pancreatic flow rate and did not modify ADPbetaS-induced relaxation. This inhibitor of the Na+/K+ pump increased the pancreatic vasoconstriction induced by L-NAME or by the co-administration of L-NAME and indomethacin. Ouabain did not modify either the L-NAME or the L-NAME/indomethacin resistant part of the ADPbetaS vasodilatation. 4. The K(ATP) inhibitor tolbutamide (185 microM) did not significantly modify basal pancreatic flow rate and ADPbetaS-induced relaxation. This inhibitor which did not change L-NAME-induced vasoconstriction, significantly diminished the L-NAME resistant part of ADPbetaS-induced vasodilatation. Tolbutamide intensified the vasoconstriction induced by the co-administration of L-NAME and indomethacin. In contrast, the L-NAME/indomethacin resistant part of ADPbetaS vasodilatation was not changed by the closure of K(ATP). 5. The SK(Ca) inhibitor apamin (0.1 microM) did not significantly change pancreatic vascular resistance whatever the experimental conditions (in the absence or in presence of L-NAME or L-NAME/indomethacin). In the presence of L-NAME, the closure of SK(Ca) channels changed the one minute vasodilator effect of ADPbetaS into a potent vasoconstriction and thereafter modified only the beginning of the second part of the L-NAME-resistant part of the ADPbetaS-induced vasodilatation. In contrast, the L-NAME/indomethacin resistant part of ADPbetaS-induced relaxation remained unchanged in the presence of apamin. 6. Charybdotoxin (0.2 microM), an inhibitor of BK(Ca), increased pancreatic vascular resistance in the presence of L-NAME/indomethacin. In the presence of L-NAME, the closure of BK(Ca) channels reversed the one minute vasodilator effect of ADPbetaS into a potent vasoconstriction and drastically diminished the sustained vasodilatation. In contrast the L-NAME/indomethacin resistant part of ADPbetaS-induced relaxation was not modified by the presence of charybdotoxin. Under L-NAME/indomethacin/charybdotoxin/apamin infusions, ADPbetaS evoked a drastic and transient vasoconstriction reaching a maximum at the second minute, which was followed by a sustained increase in the flow rate throughout the ADPbetaS infusion. The maximal vasodilator effect of ADPbetaS observed was not modified by the addition of apamin. 7. The results suggest that the L-NAME-resistant relaxation induced by ADPbetaS in the pancreatic vascular bed involves activation of BK(Ca), K(ATP) and to a lesser extent of SK(Ca) channels, but the L-NAME/indomethacin resistant part of ADPbetaS-induced relaxation is insensitive to the closure of K(ATP), SK(Ca) and BK(Ca) channels.
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PMID:Involvement of K+ channel permeability changes in the L-NAME and indomethacin resistant part of adenosine-5'-O-(2-thiodiphosphate)-induced relaxation of pancreatic vascular bed. 963 Mar 54

Experiments were designed to characterize the cellular mechanisms of action of endothelium-derived vasodilator substances in the rabbit femoral artery. Acetylcholine (ACh, 10(-8)-10(-5) M) induced a concentration-dependent relaxation of isolated endothelium-intact arterial rings precontracted with norepinephrine (NE, 10(-6) M). The ACh-induced response was abolished by the removal of endothelium. NG-nitro-L-arginine (L-NAME, 10(-4) M), an inhibitor of NO synthase, partially inhibited ACh-induced endothelium-dependent relaxation, whereas indomethacin (10(-5) M) showed no effect on ACh-induced relaxation. 25 mM KCl partially inhibited ACh-induced relaxation by shifting the concentration-response curve and abolished the response when combined with L-NAME and NE. In the presence of L-NAME, ACh-induced relaxation was unaffected by glibenclamide (10(-5) M) but significantly reduced by apamin (10(-6) M), and almost completely blocked by tetraethylammonium (TEA, 10(-3) M), iberiotoxin (10(-7) M) and 4-aminopyridine (4-AP, 5 x 10(-3) M). The cytochrome P450 inhibitors, 7-ethoxyresorufin (7-ER, 10(-5) M) and miconazole (10(-5) M) also significantly inhibited ACh-induced relaxation. Ouabain (10(-6) M), an inhibitor of Na+, K(+)-ATPase, or K(+)-free solution, also significantly inhibited ACh-induced relaxation. ACh-induced relaxation was not significantly inhibited by 18-alpha-glycyrrhetinic acid (18 alpha-GA, 10(-4) M). These results of this study indicate that ACh-induced endothelium-dependent relaxation of the rabbit femoral artery occurs via a mechanism that involves activation of Na+, K(+)-ATPase and/or activation of both the voltage-gated K+ channel (Kv) and the large-conductance, Ca(2+)-activated K+ channel (BKCa). The results further suggest that EDHF released by ACh may be a cytochrome P450 product.
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PMID:The involvement of K+ channels and the possible pathway of EDHF in the rabbit femoral artery. 1048 35

Although endothelium-derived hyperpolarizing factor (EDHF) is thought to be a cytochrome P-450 product (arachidonic acid metabolite) in some tissues, in porcine coronary arteries (PCAs) its nature remains unclear. Because phospholipase A2 and C are involved in the synthesis and/or release of EDHF in the PCA, the arachidonic acid (AA) pathway may be involved. In the presence of the cyclooxygenase inhibitor indomethacin (10(-5) M) and the NOS inhibitor Nomega-nitro-L-arginine methyl ester (L-NAME; 10(-4) M), both bradykinin (BK; 10(-9)-10(-6) M) and AA (10(-7)-10(-4) M) induced dose-dependent relaxation of PGF2alpha-contracted PCA rings, which was blocked by a high extracellular concentration of KCl (30 mM) or pretreatment with ouabain, a Na+/K+-adenosine triphosphatase (ATPase) inhibitor (5 x 10(-7) M). Eicosatetraynoic acid (ETYA; 20 microM), which inhibits all AA pathways, slightly affected the response to BK and AA; however, lipoxygenase or cytochrome P-450 inhibitors had no effect, suggesting that relaxation is independent of these enzymatic pathways. Because endothelial cells can generate reactive oxygen species (ROS) via metabolism of AA and independent of cyclooxygenase activity, we also studied (a) whether ROS can relax the PCA, as well as the mechanism(s) involved, and (b) the role of ROS in BK- and AA-induced relaxation. Xanthine (X; 100 microM) plus xanthine oxidase (XO; 0.02 U/ml) induced time-dependent relaxation of PGF2alpha-contracted PCA rings in the presence of indomethacin and L-NAME. Dilatation was not affected by superoxide dismutase (SOD; 500 U/ml) but was abolished by catalase (300 U/ml), suggesting that hydrogen peroxide (H2O2) is involved. When rings were contracted by depolarizing them with 30 mM KCl, X/XO failed to elicit relaxation. Ouabain abolished the response to X/XO, suggesting that X/XO may induce relaxation by hyperpolarizing vascular smooth muscle cells via stimulation of the Na+/K+-ATPase pump. We therefore questioned whether ROS might be involved in BK- and AA-induced relaxation. Because catalase combined with SOD had little or no effect, we concluded that in the PCA, the relaxation induced by BK via EDHF involves some mechanism independent of NO, AA metabolism, or ROS.
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PMID:Reactive oxygen species: role in the relaxation induced by bradykinin or arachidonic acid via EDHF in isolated porcine coronary arteries. 1051 Nov 33

Ouabain has been shown to be an endogenous hormone that is synthesized and released from the adrenal cortex and is present in nanomolar to subnanomolar concentrations in plasma. It has been proposed that endogenous ouabain can increase vascular resistance and induce hypertension. This substance inhibits the Na(+)-pump activity, which leads to intracellular Na+ accumulation and ultimately to increased vascular tone. It is also suggested that circulating ouabain influences the vascular smooth muscle response to vasopressor substances. However, the mechanisms by which low concentrations of ouabain influence the smooth muscle, directly or acting through the endothelium, have not been completely elucidated. We tested the hypothesis that the endothelium exerts a modulatory effect on the actions of ouabain. In these studies, isolated rat-tail vascular bed preparations obtained from normotensive animals were used. The effects of 10 nM ouabain on the reactivity of the vascular smooth muscle to phenylephrine were determined under conditions in which endothelial function was preserved or reduced by endothelial removal and treatment with N(omega)-nitroL-arginine methyl ester (L-NAME) or potassium channel blocker (tetraethylammonium; TEA). Results showed that ouabain enhanced the reactivity to phenylephrine. The enhancement of the reactivity to phenylephrine produced by ouabain was potentiated by deendothelialization and by using TEA, but it was reduced by treatment with L-NAME. The effect of 10 nM ouabain on the functional activity of the Na+,K(+)-adenosine triphosphatase (ATPase) also was evaluated. Na+,K(+)-ATPase activity was reduced after 1-h treatment with ouabain. These results suggested that low concentrations of ouabain reduced the functional activity of the Na+,K(+)-ATPase and stimulated the release of a potassium channel opener, suggesting that the effects of ouabain are partially modulated by the endothelium.
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PMID:The influence of nanomolar ouabain on vascular pressor responses is modulated by the endothelium. 1059 34

Ouabain is an endogenous compound that has been associated with the genesis and maintenance of hypertension. This compound inhibits the Na+ pump activity, which leads to an accumulation of intracellular Na and ultimately might increase vascular tone. In nanomolar concentrations, it enhances vasopressor responses to phenylephrine in some vascular beds from normotensive and hypertensive rats. However, it is not known whether this action of ouabain is a common mechanism for all models of hypertension. The aim of this work was to determine whether ouabain can alter pressor responses to phenylephrine in rats with Nomega-nitro-l-arginine methyl ester (L-NAME)-induced hypertension. In anesthetized rats, ouabain (0.18 microg/kg, i.v.) increased arterial blood pressure in L-NAME-treated rats but not in controls. Ganglionic blockade by hexamethonium (5 mg/kg, i.v.) prevented the increase in arterial blood pressure produced by ouabain in L-NAME-treated rats. Additional studies using isolated perfused tail artery preparations were performed to investigate which factors are involved in the action of ouabain in L-NAME-treated rats. The effects of 10 nM ouabain on the vasoconstrictor actions of phenylephrine were determined on preparations with intact or damaged endothelium or in the presence of tetraethylammonium (a K+-channel blocker). Ouabain reduced pressor actions of phenylephrine in preparations with an intact endothelium. However, after endothelial damage or infusing tetraethylammonium, the response to phenylephrine was increased after ouabain. In tails from L-NAME-treated rats, the functional activity of the Na, K+-ATPase was reduced, and 10 nM ouabain did not produce any further reduction. In conclusion, in this model of hypertension, a low dose of ouabain (0.18 microg/kg) increased arterial blood pressure in vivo probably as a result of increased sympathetic tone. However, this effect was not accompanied by an enhanced action of phenylephrine on the tail vascular bed with an intact endothelium. The results suggest that this was due to the release of an endothelium-derived K+-channel opener.
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PMID:Ouabain changes arterial blood pressure and vascular reactivity to phenylephrine in L-NAME-induced hypertension. 1250 28

1. This study compares the role of endothelial factors in alpha-adrenoceptor contractile responses in mesenteric resistance (MRA) and superior (SMA) mesenteric arteries from ouabain-treated (8.0 microg day(-1), 5 weeks) and untreated rats. The role of the renin-angiotensin system was also evaluated. 2. Ouabain treatment increased systolic blood pressure. In addition, ouabain reduced the phenylephrine response in SMA but did not alter noradrenaline responses in MRA. 3. Endothelium removal or the nitric oxide synthase (NOS) inhibitor (l-NAME, 100 microm) increased the responses to alpha-adrenergic agonists in both vessels. After ouabain treatment, both endothelial modulation and the l-NAME effect were increased in SMA, while only the l-NAME effect was increased in MRA. Endothelial NOS expression remained unaltered after ouabain treatment. 4. Indomethacin (10 microm) similarly reduced the noradrenaline contraction in MRA from both groups; in contrast, in SMA, indomethacin only reduced phenylephrine-induced contractions in segments from untreated rats. Co-incubation of l-NAME and indomethacin leftward shifted the concentration-response curves for noradrenaline more in MRA from ouabain-treated rats; tetraethylammonium (2 mm) shifted the noradrenaline curves further leftward only in MRA from untreated rats. 5.Losartan treatment prevents the development of hypertension but not all vascular changes observed after ouabain treatment. 6. In conclusion, a rise in endothelial NO and impaired prostanoid participation might explain the reduction in phenylephrine-induced contraction in SMA after ouabain treatment. An increase in the modulatory effect of endothelial NO and impairment of endothelium-dependent hyperpolarizing factor effect might explain why the ouabain treatment had no effect on noradrenaline responses in MRA.
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PMID:Ouabain-induced hypertension alters the participation of endothelial factors in alpha-adrenergic responses differently in rat resistance and conductance mesenteric arteries. 1530 85

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