UMLS:C0406810 - FACTA Search

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Query: UMLS:C0406810 (NAME)
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The objective of this study was to examine the influence of the endothelium on the extracellular magnesium induced relaxation of basal tension in isolated aortas from both mineralocorticoid-salt (DOCA-salt) hypertensive and control normotensive Sprague Dawley male rats. After incubation in magnesium-free physiological salt solution (PSS) (O mM magnesium), the increase of extracellular magnesium (1.2; 4.8 mM magnesium) caused a decrease in aortic tone which was significantly greater when endothelium was disrupted. Magnesium-induced relaxation was also more pronounced when endothelial NO production was blocked by 10(-4) M N omega-nitro-L arginine methyl ester (L-NAME). It is suggested that the vasorelaxation induced by extracellular magnesium is linked to the level of aortic basal tension developed in magnesium-free PSS. The endothelium does not seem to be directly implicated in magnesium-induced vasorelaxation in aortas from normotensive rats. However, in DOCA-salt hypertensive rats, the magnesium-induced relaxation of basal tension was less in the intact aorta (though not when the endothelium was disrupted) when the cyclo-oxygenase pathway was blocked by 10(-6) M indomethacin. These data therefore suggest that extracellular magnesium can promote relaxation by endothelium-dependent and cyclo-oxygenase-dependent mechanisms such as the production of relaxing prostacyclin in isolated aorta from DOCA-salt hypertensive rats.
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PMID:Influence of endothelium in the in vitro vasorelaxant effect of magnesium on aortic basal tension in DOCA-salt hypertensive rat. 129 60

1. Muscarinic stimulation of isolated, preconstricted segments of the basilar artery, with either acetylcholine or carbachol, was followed by endothelium-dependent smooth muscle relaxation and membrane hyperpolarization. 2. Smooth muscle relaxation to acetylcholine was stimulated in the presence of lower concentrations than the associated hyperpolarization (EC50 values 3.2 microM and 31.6 microM, respectively), and was sustained during agonist application, while the hyperpolarization was relatively transient. 3. Repeated exposure to acetylcholine was associated with loss of membrane hyperpolarization, while smooth muscle relaxation was unaltered. Following a second exposure to 100 microM acetylcholine, mean hyperpolarization was markedly depressed from 8.5 to 2 mV, and subsequent exposures failed to induce any hyperpolarization. Relaxations with a similar amplitude and rate of development, were recorded with each subsequent addition of acetylcholine. 4. The competitive substrate inhibitors for nitric oxide synthase, L-NG-monomethyl arginine (100 microM L-NMMA) or L-NG-nitro arginine methyl ester (100 microM L-NAME), modified the form and amplitude of both the relaxation and the hyperpolarization to acetylcholine. In the majority of experiments, both the hyperpolarization and the relaxation were almost totally abolished. 5. Neither nitric oxide, applied directly in physiological salt solution, nor sodium nitroprusside, produced smooth muscle hyperpolarization except in high concentrations. Reproducible, small amplitude (around 2 mV) hyperpolarization followed the application of either NO gas (15 microM) or sodium nitroprusside (100 microM), both of which induced almost maximal smooth muscle relaxation. 6. These data show that muscarinic stimulation of endothelial cells in the rabbit basilar artery is followed by both smooth muscle hyperpolarization and relaxation. They indicate that nitric oxide is involved in both of these responses, but that the smooth muscle hyperpolarization is not an essential component of the relaxation.
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PMID:Endothelium-dependent relaxation to acetylcholine in the rabbit basilar artery: importance of membrane hyperpolarization. 138 Mar 79

Vasorelaxant effects of magnesium (Mg) have been described in man and in animal with arterial hypertension. Some studies have shown relationships between extracellular Mg (magnesium e.c.) and endothelial function. So, our study is designed to determine whether elevated extracellular Mg leads to an endothelium-dependent vasorelaxant effect on contractile tension developed by noradrenaline in isolated aorta from DOCA-salt hypertensive rats. Elevated extracellular Mg (4.8 mM) in the bath significantly depressed the dose-response curve to noradrenaline in aorta with endothelium. Following disruption of endothelium, the vasorelaxant effect of elevated extracellular Mg on contractile response to noradrenaline was greatly inhibited. Furthermore, in presence of L. NG nitroarginine (L-NAME) (10(-4) M), inhibitor of endothelial nitric oxide (NO) biosynthesis, the vasorelaxant effect of extracellular Mg on contractility to noradrenaline was partially inhibited. The addition of sodium nitroprussiate (5 10(-9) M), known to spontaneously release NO, caused the reappearance of Mg vasorelaxation which had disappeared in aorta without endothelium. In conclusion, vascular endothelium seems to play an important role in the Mg-induced depressed contractile response to noradrenaline in isolated aorta from DOCA-salt hypertensive rat. Endothelial NO seems to be implicated in the endothelium-dependent action of extracellular Mg.
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PMID:[In vitro study of the role of endothelium on the vasorelaxant effect of magnesium on the aorta from DOCA-salt hypertensive rats]. 148 62

Hypercholesterolemia is associated with increased oxidized LDL and impaired endothelium-dependent relaxation (EDR). An inhibitory component of oxidized LDL is lysophosphatidylcholine (LPC). To determine the effect and mechanism(s) of action of LPC on EDR mediated by endothelium-derived nitric oxide (EDNO) and endothelium-derived hyperpolarizing factor (EDHF), rabbit abdominal aortic rings were suspended for measurement of isometric tension and studied under three conditions: control; with 25 mmol/L K+ buffer to isolate relaxation mediated by EDNO; and in rings treated with N omega-nitro-L-arginine methyl ester (L-NAME, 30 mumol/L) to isolate relaxation mediated by EDHF. Incubation with LPC (10 and 30 mumol/L) for 30 minutes inhibited EDR in a concentration-dependent manner. LPC (30 mumol/L) significantly inhibited maximal relaxation to acetylcholine in control, 25 mmol/L K(+)-, and L-NAME-treated rings (77.1 +/- 7.8%, 42.1 +/- 8.9%, and 3.4 +/- 7.7%) compared with untreated rings (99.0 +/- 0.9%, 90.9 +/- 2.2%, and 54.7 +/- 4.7%, P < .05). Inhibition of relaxation was specific to endothelium-dependent responses in that relaxation to direct smooth muscle vasodilators (papaverine, 8-bromo-cGMP, and sodium nitroprusside) were unaltered by LPC. The inhibition by LPC (30 mumol/L) was not due to cytotoxicity, because EDR returned to normal levels after repeated washing with physiological salt solution containing 0.1% albumin. Co-incubation with protein kinase C inhibitors, staurosporine (20 nmol/L) or calphostin C (1 mumol/L), had no effect on the EDR inhibition by LPC (30 mumol/L). Furthermore, LPC continued to inhibit EDR in rings in which protein kinase C was down-regulated by incubation for 18 hours with 1 mumol/L phorbol 12-myristate 13-acetate (PMA).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lysophosphatidylcholine inhibits relaxation of rabbit abdominal aorta mediated by endothelium-derived nitric oxide and endothelium-derived hyperpolarizing factor independent of protein kinase C activation. 748 55

The contribution of the renin-angiotensin system (RAS) and various endogenous vasoconstrictors on the pressor response to acute N omega-nitro-L-arginine methyl ester (L-NAME) administration (200 micrograms/kg/min) was assessed in anesthetized Wistar rats. Activity of the endogenous RAS was suppressed either by chronic treatment by a nonpeptide angiotensin II (AII) receptor antagonist (losartan) or an angiotensin-converting enzyme inhibitor (ACEI: enalapril), DOCA-salt pretreatment (without previous uninephrectomy), and binephrectomy (36-40 hours before experiments). We also studied the influence of chronic dietary sodium restriction. The role of alpha 1-adrenoceptor activity, endothelin (ET), and eicosanoids was evaluated in rats pretreated by prazosin, phosphoramidon (a nonspecific blocker of the conversion of big ET to ET), indomethacin, and the thromboxane A2 (TXA2) prostaglandin H2 (PGH2)-receptor antagonist SQ 29548, respectively. Finally, we tested the influence of the calcium channel blocker nicardipine on the vasopressor effect of L-NAME. In nonpretreated animals, L-NAME infusion induced an increase in mean arterial pressure (MAP) of 38 +/- 4 mm Hg. Chronic suppression of the RAS by losartan, enalapril, or DOCA did not alter the response to L-NAME, but the effect of L-NAME was moderately blunted in binephrectomized rats. Moderate attenuation (approximately 25%) and to a similar extent of the pressor effect of L-NAME was afforded by the low-sodium diet, phosphoramidon, SQ 29548, and indomethacin, whereas nicardipine markedly blunted by 74% the effect of L-NAME. We conclude that the acute pressor effect of L-NAME is mediated (at least in part) by cyclooxygenase-dependent products (mainly TXA2) and ET, but not by the RAS.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Endogenous vasoactive systems and the pressor effect of acute N omega-nitro-L-arginine methyl ester administration. 752 59

Endogenous nitric oxide plays an important role in modulation of renal hemodynamics and sodium handling, with increased nitric oxide production inducing renal vasodilation and natriuresis. In the normal rat, nitric oxide activity increases as an adaptive response to increased dietary salt intake, perhaps facilitating natriuresis and thus blood pressure homeostasis. We hypothesized that impaired nitric oxide synthetic ability would result in sensitivity to the pressor effects of high dietary salt intake. Four groups of normal Sprague-Dawley rats were observed for eight weeks: Control, 0.4% NaCl chow and tap water; Salt, 4% NaCl chow and tap water; NAME, 0.4% NaCl chow and water containing the nitric oxide synthase inhibitor, L-nitro-arginine-methylester; Salt+NAME, 4% NaCl chow and water containing L-nitro-arginine-methylester. Compared to Controls, Salt rats demonstrated a significant increase in urinary excretion rate of the stable nitric oxide metabolites, NO2 and NO3, and had no increase in blood pressure. Furthermore, Salt rats had no functional or structural evidence of renal injury. In contrast, Salt+NAME rats demonstrated a significantly higher blood pressure than NAME rats, and urinary NO2 and NO3 excretion rate did not increase despite high salt intake. After eight weeks, Salt+NAME rats had significantly impaired renal function and proteinuria. We conclude that adaptive changes in endogenous NO production play a critical role in sodium and blood pressure homeostasis. Furthermore, impaired nitric oxide synthase activity may be a pathogenetic factor in the development of salt-sensitive hypertension.
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PMID:Endogenous nitric oxide synthesis determines sensitivity to the pressor effect of salt. 752 54

Since dietary salt loading enhances nitric oxide (NO) generation in the kidney, we investigated the hypothesis that changes in salt intake have specific effects on vascular resistance in the kidney mediated by the L-arginine-NO pathway. We contrasted changes in renal and hindquarter vascular resistances (RVR and HQVR) in anesthetized rats during intravenous infusions of graded doses of the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). Groups (N = 8 to 10) of rats were maintained on a high salt (HS) or low salt (LS) diet for two weeks. Compared to those on LS, rats on HS had a greater increase in mean arterial pressure (delta MAP; +32 +/- 4 vs. +22 +/- 3%; P = 0.05) and RVR (+160 +/- 17 vs. +83 +/- 10%; P < 0.005) and a greater fall in renal blood flow (delta RBF; -47 +/- 3 vs. -32 +/- 4%; P < 0.01); changes in HQVR were similar in the two groups. The enhanced RVR response to L-NAME in HS rats could not be ascribed to the higher renal perfusion pressure (RPP) since it persisted in rats whose RPP was controlled by adjustment of a suprarenal aortic clamp. Changes in RVR with an NO donor (SIN-1) were similar in HS and LS rats. L-NAME reduced plasma renin activity in both HS and LS rats. After inhibition of ACE with captopril, or of angiotensin II type I (AT1) receptor with losartan, the increase in RVR with L-NAME remained greater in HS than LS rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Renal vasoconstriction during inhibition of NO synthase: effects of dietary salt. 752 72

We describe a simple, functional approach to defining the relative contribution of endothelium-dependent hyperpolarization (presumably mediated by a factor, EDHF) and endothelium-derived nitric oxide (EDNO) to acetylcholine (ACh) and histamine relaxations of isolated perfused rat mesenteric resistance arterial bed. In physiologic salt solution (PSS), ACh- and histamine-induced vasodilations of cirazoline-preconstricted mesenteric arterial bed were only partially attenuated by 50 microM Nw-nitro-L-arginine methyl ester (L-NAME). The L-NAME-resistant component was abolished by 0.5 microM apamin but not by 250 nM dendrotoxin or 10 microM glyburide, thus indicating a role for apamin-sensitive K+ channels in mediating the effects of the putative EDHF. Changing membrane potential by varying [K+] decreased L-NAME-resistant vasodilation, and showed a modest L-NAME-induced increase in the basal perfusion pressure that was not observable in normal PSS. Vasodilator responses during cirazoline-induced tonus in 20 mM K+ and normal PSS were superimposable, but responses to ACh and histamine in 20 mM K+ were profoundly more sensitive to L-NAME than were those in normal PSS media. ACh responses during 20-mM K+ PSS perfusion and presumably mediated by EDNO and those resistant to L-NAME and putatively mediated by EDHF were antagonized by graded concentrations of p-fluorohexahydro-siladifenidol (p-F-HHSiD), but not pirenzepine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Varying extracellular [K+]: a functional approach to separating EDHF- and EDNO-related mechanisms in perfused rat mesenteric arterial bed. 768 3

In this study we have continuously measured real-time production of nitric oxide (NO) in the isolated, perfused rat lung by using an NO monitor (model NO-501, Inter Medical Co., Nagoya, Japan) with an NO-selective resin microsensor. A stable NO response was obtained when the sensor was placed in the pulmonary artery or the pulmonary vein; in contrast, the tracings obtained from the lung periphery were unstable. Furthermore, the NO release was higher when the isolated lungs were perfused with physiological salt solution rather than whole blood perfusion. Changes in NO production were also monitored in acute hypoxia and reoxygenation. Pretreatment with endotoxin (10 mg/kg) potentiated the NO release observed, and this effect of endotoxin was further potentiated by arginine (1 x 10(-4) M) and acetylcholine (1 x 10(-5) M) and countered by the NO synthase inhibitor, L-NG-nitro-arginine methyl ester (L-NAME; 1 x 10(-3) M).
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PMID:Measurement of nitric oxide release in the isolated perfused rat lung. 770

1. The inherent contractile tone, and its modulation by the endothelium, have been studied in isolated pulmonary artery preparations taken from rats in which pulmonary hypertension was induced by exposure to a hypoxic environment (10% O2) for 14 days. Control rats were housed in room air. 2. All preparations in which the endothelium was left intact relaxed in response to acetylcholine (43 +/- 4% and 54 +/- 9%, reversal of the noradrenaline-induced contraction in control and hypoxic rats, respectively) indicating that the endothelium was functional in both groups of rats. 3. Exposure of the preparations to Ca(2+)-free physiological salt solution containing 2 mM EGTA for 30-40 min had no effect on preparations from control rats but caused relaxation in preparations from hypoxic rats. The relaxation (taken as a measure of the inherent tone in the preparations) was larger in preparations without endothelium (14.5 +/- 1.9 mN mm-2; n = 5) than in preparations with endothelium (9.1 +/- 1.2 mN mm-2; n = 5). 4. In preparations from hypoxic rats the magnitudes of the contractions to 80 mM K+ and to noradrenaline (0.1 microM) were less than in preparations from control rats. This may have been because the preparations from hypoxic rats were already partially contracted due to the inherent tone. 5.The nitric oxide (NO) synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 0.1-1 100 microM)had negligible effect on preparations from control rats or on endothelium-denuded preparations from hypoxic rats, but produced concentration-dependent contractions (maximum contraction 7.4 +/- 0.7 mN mm-2 (n = 4) with 100 micro M) in endothelium-intact preparations from hypoxic rats. This effect of L-NAME was prevented by L-arginine (1 mM) but not by D-arginine (1 mM).6. Contractions to L-NAME were also seen in endothelium-intact arteries from control rats if the preparations were first partially contracted by exposure to K+, endothelin, U46619 (thromboxane mimetic)or noradrenaline.7 It is concluded that isolated pulmonary artery rings from hypoxic rats, but not those from control rats, have substantial inherent tone. This inherent tone is normally attenuated by the generation of an endothelium-derived factor that is probably NO. A stimulus for the release of NO from the endothelium may be the contraction of the underlying smooth muscle, whether the contraction is inherent in the tissue, as in preparations from hypoxic rats, or is induced by a vasoconstrictor spasmogen.
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PMID:Evidence that nitric oxide from the endothelium attenuates inherent tone in isolated pulmonary arteries from rats with hypoxic pulmonary hypertension. 771 5

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