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. An isolated, buffer-perfused rabbit ear preparation was used to investigate the influence of NG-nitro-L-arginine methyl ester (L-NAME) on endothelium-dependent vasodiltation and modulation of vasoconstrictor responses and vascular conductance. 2. Acetylcholine (0.55 pmol-1.6 nmol) caused dose-related vasodilatation of preparations constricted by the combination of 5-hydroxytryptamine and histamine (both 1 microM), with an ED50 = 31.1 +/- 7.8 pmol and a maximum dilatation of 69.9 +/- 4.3%. In the presence of 10 microM L-NAME the dose-response for vasodilator effects was shifted significantly (P less than 0.001) to the right (ED50 = 3.07 +/- 1.18 nmol) and there was a significant (P less than 0.01) depression of the maximum response (Rmax = 44.3 +/- 4.0%). The higher concentration of 100 microM L-NAME completely abolished vasodilatation to acetylcholine. L-Arginine (10 mM) did not reverse the inhibitory actions of L-NAME at either concentration. 3. L-NAME 100 microM, augmented vascular tone induced by 1 microM 5-hydroxytryptamine and 1 microM histamine, thus altering the characteristics of both pressure/flow and conductance/flow relationships such that conductance was reduced at all flow rates. The augmentation of constrictor tone was reversed in a concentration-dependent manner by L-arginine (10 microM-10 mM) and the effect of L-NAME on the conductance/flow relationships was similarly reversed by 10 mM L-arginine. The augmentation of tone was endothelium-dependent as it did not occur following functional destruction of the endothelium by perfusion of the vascular bed with the detergent CHAPS (0.3%) for 150s. 4. In conclusion, L-NAME is a potent inhibitor of agonist-induced endothelium-dependent vasodilatation. L-NAME reduces vascular conductance in pharmacologically constricted preparations and this emphasizes the important role of EDRF in vascular regulation. The ability of L-arginine to reverse L-NAME-induced inhibition of basal EDRF activity but not L-NAME-induced inhibition of agonistinduced endothelium-dependent relaxations suggests that there is pharmacological heterogeneity in the mechanisms responsible for the conversion of L-arginine to EDRF.
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PMID:Differential effects of L-arginine on the inhibition by NG-nitro-L-arginine methyl ester of basal and agonist-stimulated EDRF activity. 179 35

1. The isolated superior mesenteric arterial bed of the rat, perfused with Krebs-Henseleit solution containing 10 microM indomethacin, was used to study the effects of reducing dissolved O2 tension on the pressor responses to endothelin-1, endothelin-3 and sarafotoxin S6b. The modulation of these responses by the endothelium was investigated by removing the intima with the detergent CHAPS and, for endothelin-1, by inhibiting nitric oxide production with N omega-nitro-L-arginine methyl ester (L-NAME). Comparison was made with the effects of lowering O2 tension on the pressor responses to noradrenaline and 5-hydroxytryptamine. 2. Lowering the perfusate O2 tension from 551 +/- 2 mmHg to 14.0 +/- 0.5 mmHg did not change the ED50 for endothelin-1 but its maximal responses (Rmax) were increased by 2.1 and 2.7 fold, respectively, in the presence and absence of endothelium. The Rmax values for endothelin-3 were also greater in hypoxia either in the presence (by 2.3 fold) or absence of the endothelium (by 1.6 times) but those for sarafotoxin S6b were only enhanced significantly by hypoxia in the absence of the intima. hypoxia reduced the potencies of endothelin-3 and sarafotoxin S6b whether or not endothelium was present. 3. Endothelial destruction, whether in hypoxic or oxygenated conditions, increased the Rmax values for endothelin-1 and endothelin-3; at both O2 tensions those for endothelin-3 increased more than those for endothelin-1. The ED50 for endothelin-1 was unchanged by destroying the endothelium but endothelin-3 was less potent in the absence of an endothelium than in its presence. Removal of the endothelium did not change the R.ax for sarafotoxin S6b but increased its potency in both hypoxic and oxygenated tissues. 4. In hypoxia, and in the presence of both the endothelium and 100 microM L-NAME, the Rmax for endothelin-1 was 1.6 times greater than that in hypoxia in the absence of L-NAME. Co-infusion of 100 microM L-arginine, but not of 100 mircoM D-arginine, with 100 microM L-NAME reversed this effect. The presence of L-NAME decreased the potency of endothelin-1. 5. Destroying the endothelium did not affect the Rmax for noradrenaline in either oxygenated conditions or hypoxia. Changing 02 tension when the endothelium was intact had no effect on the Rmax but it was 11% greater in oxygenated, than in hypoxic, endothelium denuded preparations. Endothelial destruction decreased the potency of noradrenaline in hypoxia but increased it in oxygenated tissues. In hypoxia, L-NAME had no effect on the ED50 relative to control preparations with endothelium but the Rmax was 30% greater. 6. 5-Hydroxytryptamine gave very small pressor responses in the presence of endothelium in both oxygenated and hypoxic tissues but the Rmax was 1.7 times greater in hypoxia. L-NAME increased the R,,x by 9.8 times in oxygenated preparations and 6.3 fold in hypoxia. The ED5o values were the same in all conditions. 7. It is concluded that, although hypoxia generally increased the R.. for the endothelin/sarafotoxin peptides, the changes could not be explained by a simple increase in receptor number since hypoxia decreased the potency of endothelin-3 and sarafotoxin S6b. Thus alterations in receptor binding or activation properties, or both, also occurred. The changes associated with hypoxia were not common to all vasoconstrictor agonists since, in the absence of endothelial function, hypoxia did not affect the Rmax values for either noradrenaline or 5-hydroxytryptamine. Also, the pressor responses to the peptides and both the amines can be modulated by the endothelium in hypoxia as well as in oxygenated conditions.
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PMID:Endothelial modulation and changes in endothelin pressor activity during hypoxia in the rat isolated perfused superior mesenteric arterial bed. 188 99

1. We have examined the effects of nitric oxide inhibition, indomethacin and the dual lipoxygenase/cyclo-oxygenase inhibitor, 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW755C), on the responses of small mesenteric arteries of Wistar rats, with and without endothelium, to noradrenaline, potassium chloride, endothelin-1, acetylcholine and sodium nitroprusside. 2. Noradrenaline, potassium chloride and endothelin-1 caused concentration-dependent contraction of small mesenteric arteries. Indomethacin (14 microM) attenuated the contractile response to both noradrenaline and potassium chloride. The inhibitory action of indomethacin persisted in vessels treated with CHAPS. 3. Acetylcholine produced concentration-dependent relaxation in these vessels. Indomethacin (14 microM) had no significant effect on the acetylcholine concentration-response relationship. 4. NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) potentiated the contractile response to both noradrenaline and potassium chloride and inhibited acetylcholine-induced relaxation. Indomethacin attenuated the effects of L-NAME. 5. BW755C inhibited the contractile response to noradrenaline and potassium chloride but not to endothelin-1. The inhibitory effects of BW755C persisted in the presence of indomethacin and in vessels treated with CHAPS. 6. BW755C enhanced endothelium-dependent relaxation, as assessed by the response to acetylcholine. In the presence of indomethacin, BW755C produced a shift to the right of the concentration-response curve to acetylcholine. 7. Inhibition of nitric oxide synthase with L-NAME, reversed the inhibitory effect of BW755C on noradrenaline- and potassium-induced contraction. L-NAME and BW755C in combination resulted in a shift to the right of the concentration-response curve to acetylcholine. 8. Sodium nitroprusside produced concentration-dependent relaxation of the vessels. Endothelium removal reduced the maximum relaxation to nitroprusside. BW755C did not alter the response to sodium nitroprusside in vessels with or without endothelium.9 .These data support the existence of two vasoconstrictor products of arachidonic acid released during contraction of small mesenteric arteries with noradrenaline and potassium chloride: a cyclo-oxygenase product and a lipoxygenase product both of which appear to be largely endothelium-independent.
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PMID:Interdependence of contractile responses of rat small mesenteric arteries on nitric oxide and cyclo-oxygenase and lipoxygenase products of arachidonic acid. 752 Dec 54

1. In the present work, we have studied the microvascular reactivity of the arterial and venous mesenteric beds of the guinea-pig to bradykinin, neurokinins and other agents. 2. The vasoactive properties of three selective agonists for neurokinin receptors, namely [Sar9, Met (O2)11]SP (NK1), [beta-Ala8]NKA(4-10) (NK2) and [MePhe7]NKB (NK3), were evaluated on precontracted arterial and venous mesenteric vasculatures of the guinea-pig. The NK1-selective agonist, [Sar9,Met(O2)11]SP (1 to 1000 pmol), induced an endothelium-dependent and N omega-nitro-L-arginine methyl ester (L-NAME)-sensitive relaxation of the arterial vasculature precontracted with methoxamine, whereas the NK2 and NK3-selective agonists were virtually inactive at high doses (1000 pmol). 3. The three selective neurokinin receptor agonists were inactive in the non-precontracted arterial and venous mesenteric vasculatures as well as in the precontracted venous mesenteric vasculature. 4. Bradykinin (0.1 to 100 pmol) induced a marked dose- and endothelium-dependent vasodilatation of the precontracted arterial and venous vasculatures. ED50 values were 5.5 pmol on the arterial side and 1.9 pmol on the venous side. In contrast, desArg9-bradykinin was inactive at doses up to 1000 pmol. Furthermore, on the arterial and venous sides, a higher dose of bradykinin (1000 pmol), induced a biphasic effect, a transient constriction followed by a marked and sustained vasodilatation. The vasodilator effects of bradykinin were abolished by Hoe 140 (0.1 microM) and CHAPS, markedly reduced by L-NAME and were unaffected by [Leu8]desArg9-bradykinin (0.1 microM) on both sides of the mesenteric vasculature. Hoe 140 also abolished the arterial vasoconstrictions induced by high doses of bradykinin. 5. Noradrenaline, angiotensin II and endothelin-1 produced contractions on both sides of the mesenteric circulation, while acetylcholine (arterial side) and sodium nitroprusside (arterial and venous sides) caused vasodilatation.6. Our study supports the view that NK1 receptors responsible for vasodilatation are present solely in the endothelium of the arterial mesenteric vasculature of the guinea-pig. On the other hand, bradykinin(0.1 to 100 pmol) exerts predominantly vasodilator effects on both sides of the mesenteric vasculature via selective activation of B2 receptors located on the endothelium. The same receptor type located on the smooth muscle appears to be responsible for the arterial and venous constriction with high doses of bradykinin.
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PMID:Characterization of receptors for kinins and neurokinins in the arterial and venous mesenteric vasculatures of the guinea-pig. 758 63

1. We have examined the effects of inhibition of nitric oxide synthase, cyclo-oxygenase and lipoxygenase on the responses of renal arcuate arteries of Wistar rats, with and without endothelium, to noradrenaline, potassium chloride, endothelin-1, acetylcholine and sodium nitroprusside. 2. Noradrenaline, potassium chloride and endothelin-1 caused concentration-dependent contraction of the vessels. Indomethacin (14 microM) attenuated the contractile response to noradrenaline and to potassium chloride. The inhibitory effect of indomethacin persisted following endothelial removal. 3. Acetylcholine produced concentration-dependent relaxation of the vessels which was potentiated by indomethacin (14 microM). 4. NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) did not affect the contractile response to either noradrenaline or potassium chloride but abolished relaxation to acetylcholine. In addition, L-NAME abolished the affects of indomethacin on acetylcholine-induced relaxation and noradrenaline- and potassium chloride-induced contraction. 5. BWC755C attenuated noradrenaline and potassium chloride-induced contraction. This effect persisted in the presence of indomethacin. 6. In vessels pretreated with CHAPS, BW755C inhibited both noradrenaline and potassium chloride-induced contraction. In these vessels BW755C had no additional inhibitory effect to indomethacin on noradrenaline- and potassium-induced contraction. 7. Inhibition of nitric oxide synthase with L-NAME (100 microM) attenuated the effect of BW755C on noradrenaline- and potassium-induced contraction. 8. BW755C alone did not affect endothelium-dependent relaxation as assessed by the response to acetylcholine. However, in the presence of indomethacin, BW755C inhibited acetylcholine-induced relaxation. 9. BW755C did not affect endothelium-independent relaxation as assessed by the response to sodium nitroprusside in vessels with or without endothelium. 10. These data support the existence of two vasoconstrictor products of arachidonic acid released during contraction of renal arcuate arteries with noradrenaline and potassium chloride. A cyclooxygenase product which appears to be endothelium-independent and the other an endothelium dependent lipoxygenase product.
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PMID:Relative roles of nitric oxide and cyclo-oxygenase and lipoxygenase products of arachidonic acid in the contractile responses of rat renal arcuate arteries. 807 54

The therapeutical use of cyclosporine A (CsA) is hampered by the development of nephrotoxicity characterized by a marked increase in renal vascular resistance (RVR). We investigated vascular functions in kidneys of rats treated with CsA. The ex vivo vascular reactivity of kidneys from control rats and animals treated subacutely with CsA [50 mg/kg/day subcutaneously (s.c.) for 16-21 days] or an olive oil vehicle (1 ml/kg) was analyzed in male Wistar rats. The right kidney was isolated and perfused with Tyrode's or Krebs solution in an open circuit. The effects of acetylcholine (Ach), fenoldopam (FEN), and sodium nitroprusside (SNP) on norepinephrine (NE) preconstricted kidneys were studied. In control kidneys (untreated or vehicle-treated), Ach induced a relaxation (EC50 = 0.56 +/- 0.05 x 10(-9)M; Emax = 88.2 +/- 2.1% decrease in the vascular tone restored by NE) which was endothelium-dependent [near-complete abolition after treatment with a detergent, 3-[(3-cholamidopropyl)-dimethyl-ammonio]-1-propane-sulfonate (CHAPS) treatment] but only partially inhibited by indomethacin (EC50 = 1.71 +/- 0.39 x 10(-9)M, p < 0.05; Emax = 87.1 +/- 4.9%, NS) or indomethacin with NG-nitro-L-arginine methyl ester (L-NAME: EC50 = 1.04 +/- 0.38 x 10(-9)M, NS; Emax = 63.8 +/- 2.5%, p < 0.01). CsA treatment induced a marked decrease in creatinine clearance and natriuresis measured in vivo but had no effect on systolic blood pressure (SBP). In CsA-treated rats, Ach-induced renal relaxation was partially blunted (EC50 = 1.88 +/- 0.34 x 10(-9)M, p < 0.01; Emax = 82.8 +/- 4.6, NS), with both a defect in prostaglandin (PG) and nitric oxide (NO)-related responses. CsA treatment had no effect on endothelium-independent relaxations induced by FEN and SNP. These results show that subacute CsA treatment selectively impairs renal endothelium-dependent relaxation related to PGs and NO release.
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PMID:Endothelium-dependent relaxation in the isolated rat kidney: impairment by cyclosporine A. 860 21

The aim of this study was to compare the effects of the blockade of nitric oxide (NO) and of endothelium-derived hyperpolarizing factor (EDHF) on the response to vasoconstrictors (VC) and on the flow-pressure curve in the isolated perfused rat kidney. To this end, dose-response curves to phenylephrine and BaCl2 were studied in the renal vasculature under basal conditions and after the infusion of N(omega)-nitro-L-arginine methyl ester (L-NAME) and tetraethylammonium (TEA) in endothelium-intact and endothelium-denuded (CHAPS-treated) preparations. In another experiment, renal flow-pressure curves were obtained under basal conditions and after the infusion of L-NAME or TEA. The flow-pressure curve was obtained by increasing renal perfusion flow (RPF) from 2.5 to 15 ml/min/g kidney weight (KW) over the basal level (5 ml/min/g KW). L-NAME or TEA produced a leftward shift of the dose-response curves of both VC, and the simultaneous administration of L-NAME and TEA produced a greater shift to the left in the pressor response curves. CHAPS treatment produced a leftward shift of the dose-response curves of both VC, and the dose-response curves were not significantly modified by the infusion of L-NAME or TEA. L-NAME markedly shifted the flow-pressure curve upward, especially at higher levels of RPF. However, the administration of TEA, perfusate solution (Tyrode) or D-NAME did not significantly change the flow-pressure curve. These results suggest that NO is released in response to VC as well as to increased perfusion flow in the isolated renal vascular bed. However, EDHF release seems to be stimulated by VC but not by increased perfusion flow.
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PMID:Modulatory role of endothelium-derived relaxing factors on the response to vasoconstrictors and flow-pressure curve in the isolated perfused rat kidney. 863 Mar 44

The study was designed to assess the influence of either nitric oxide (NO) or sodium nitroprusside and the absence of endothelium on the intrinsic elastic properties of coronary arteries from WKY rats. For this purpose, segments of the right interventricular coronary were mounted in an arteriograph where wall thickness and internal diameter were continuously monitored while intraluminal pressure was controlled in the absence of flow. To study the passive properties, pressure-diameter relationships were determined by measuring the corresponding internal diameter for each stepwise increase in intraluminal pressure. Thus, wall stress, strain and incremental elastic modulus (Einc) were assessed in the following experimental conditions: control, incubation with nitro-L-arginine methyl ester (L-NAME, 100 microM) or L-NAME + L-arginine (L-arg, 100 microM), incubation with sodium nitroprusside (SNP, 100 microM), endothelium removal (CHAPS). The Einc-stress relationship was not significantly different in the different experimental conditions, but values of Einc plotted as function of strain were significantly decreased after L-NAME incubation and partly reversed after L-arg addition. The same effect was observed after endothelium destruction but to a lesser extent. After SNP incubation, values of Einc were significantly decreased for small values of strain and increased for high values of this parameter. These results show that NO synthase inhibition induced, for a given strain, a decrease of elastic modulus in coronary arteries. It can be speculated that functional antagonism exerted by NO against spontaneous contractile tone was reduced. Thus, the smooth muscle cells were in a greater state of activation and probably more strongly involved in the intrinsic elastic properties of this preparation. However, an unexplained effect of NO on wall stiffness cannot be excluded. Conversely, SNP increased the initial diameter and induced an initial decrease in stiffness followed by a subsequent increase. After endothelium destruction, stiffness was significantly decreased compared to control conditions. It can be concluded that NO modulates the intrinsic elastic properties of the coronary arteries through smooth muscle cell relaxation. Furthermore, results with SNP support the hypothesis that the lower the state of activation of the smooth muscle cells, the higher the elastic modulus of the arterial wall in this coronary artery preparation.
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PMID:Effects of nitric oxide and sodium nitroprusside on the intrinsic elastic properties of pressurized rat coronary artery. 873 56

1. We have used the isolated buffer-perfused mesenteric arterial bed of the rat to assess the modulation of vasorelaxation to potassium channel openers (KCOs) by basal nitric oxide. 2. The dose-response curves to the KCOs, levcromakalim and pinacidil, in preconstricted preparations were significantly shifted to the left in the presence of the nitric oxide synthase inhibitor (100 microM) NG-nitro-L-arginine methyl ester (levcromakalim, ED50 = 4.47 +/- 0.70 nmol vs. 1.73 +/- 0.26 nmol, P < 0.001; pinacidil, ED50 = 16.1 +/- 4.8 nmol vs. 5.43 +/- 1.10 nmol, P < 0.001). The vasorelaxant responses to papaverine, a vasodilator which acts independently of potassium channels was unaffected by NG-nitro-L-arginine methyl ester (L-NAME). 3. Removal of the endothelium, by perfusion with the detergent CHAPS (0.3%), significantly (P < 0.001) increased the potency of levcromakalim as a vasodilator (ED50 4.47 +/- 0.70 nmol vs. 2.59 +/- 0.31 nmol). The subsequent administration of L-NAME following perfusion with CHAPS did not lead to any additional enhancement of responses to levcromakalim. 4. The presence of the non-selective adenosine antagonist, 8-phenyltheophylline (8-PT, 10 microM) significantly (P < 0.001) shifted the dose-response curve to levcromakalim to the left (ED50 4.47 +/- 0.70 nmol vs. 1.11 +/- 0.32 nmol). In the presence of both L-NAME and 8-PT, the dose-response curve to levcromakalim was also significantly (P < 0.01) shifted to the left compared with control (ED50 in the presence of both L-NAME and 8-PT was 0.42 +/- 0.08 nmol). 5. The presence of 8-bromo cyclic GMP (10 microM) reversed the increase potency of levcromakalim, observed following inhibition of nitric oxide synthase (ED50 in the presence of L-NAME was 0.59 +/- 0.01 nmol and in the presence of 8-bromo cyclic GMP plus L-NAME the ED50 was 3.17 +/- 0.80 nmol). However in the absence of L-NAME, the cell permeable analogue of cyclic GMP, 8-bromo cyclic GMP, did not affect the dose-response curve to levcromakalim compared with control (control ED50 value was 4.16 +/- 0.52 nmol vs. 3.85 +/- 1.13 nmol in the presence of 8-bromo cyclic GMP). 6. The present investigation demonstrates that both basal nitric oxide and adenosine modulate vasorelaxation to the KCOs levcromakalim and pinacidil. The modulatory effect of nitric oxide may be mediated via cyclic GMP.
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PMID:Modulation of vasorelaxant responses to potassium channel openers by basal nitric oxide in the rat isolated superior mesenteric arterial bed. 885 2

We have tested the vasoactive effects of kinins in addition to various other endothelium-dependent or independent agonists in the arterial and venous perfused mesenteric circuits of the mouse. Bradykinin (0.1 pmol-100 nmol), but not des-Arg9-bradykinin (10 nmol) induced a dose-dependent vasodilation of the precontracted arterial and venous mesenteric vasculature of the mouse. Furthermore, acetylcholine (2.5 nmol) also induced a marked arterial vasodilation but was without effect on the venous side. Other endothelium-dependent vasodilators, such as platelet-activating factor (PAF) (1 nmol), tachykinin NK1 selective agonist ([Sar9,Met(O2)(l1) ]substance P) (0.5 nmol) and adenosine diphosphate (5 nmol), were without effect on either side of the mesenteric bed of the mouse. The bradykinin B2 receptor selective antagonist (HOE 140) abolished the arterial and venous vasodilation induced by bradykinin without affecting that of acetylcholine or sodium nitroprusside. In addition, the bradykinin B1 receptor antagonist des-Arg9-[Leu8]bradykinin was without effect on the responses induced by bradykinin. A nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) markedly reduced, whereas removal of the endothelium with 3-[3-cholamidopropyl)dimethylammonio]-1-propane sulfonate (CHAPS) abolished dilatation to bradykinin and acetylcholine (arterial side only) without affecting that induced by sodium nitroprusside in the mouse arterial and venous mesenteric circuits. In the same two circuits of transgenic B2 knockout mice, the vasodilatory responses to bradykinin were absent, whereas the arterial circuit still responded to acetylcholine by a L-NAME-sensitive vasodilation. Our results suggest the exclusive contribution of B2 receptors located on the endothelium in the vasodilatory effects of bradykinin in the arterial and venous mesenteric circuits of the mouse.
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PMID:Pharmacology of kinins in the arterial and venous mesenteric bed of normal and B2 knockout transgenic mice. 931 61

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