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

Nitric oxide is an important regulator of vascular function and blood pressure. Chronic administration of nitric oxide inhibitors provides a new model of hypertension with pronounced target organ damage. We investigated the effects of oral treatment with N omega-nitro-L-arginine methyl ester (L-NAME) for 6 weeks on vascular reactivity of the aorta in Wistar-Kyoto rats. Certain rats received verapamil or trandolapril in addition to L-NAME. Systolic blood pressure increased in the L-NAME group (by approximately or equal to 80 mm Hg systolic) but not in controls or rats treated with verapamil or trandolapril. Isometric tension changes of aortic rings were recorded. Endothelium-dependent relaxations to acetylcholine were reduced in the L-NAME group (58 +/- 6% versus 104 +/- 1% in placebo, P < .05) but were normalized by treatment with verapamil or trandolapril. In contrast, endothelium-independent relaxations to sodium nitroprusside were not significantly reduced in L-NAME hypertension but were slightly enhanced by trandolapril therapy (P < .05) in the L-NAME group only. In quiescent rings, acetylcholine caused endothelium-dependent contractions in particular after in vitro incubation with L-NAME. These contractions tended to be enhanced in L-NAME hypertension (23 +/- 4% versus 14 +/- 3% in the placebo group; P = NS) and were significantly reduced after treatment with verapamil or trandolapril (P < .05). Concentrations to norepinephrine and angiotensin I and II were unaffected by L-NAME hypertension, whereas those to endothelin-1 were reduced (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:L-NAME hypertension alters endothelial and smooth muscle function in rat aorta. Prevention by trandolapril and verapamil. 759 Oct 13

To determine whether inhibition of generation of endothelium-derived relaxing factor or nitric oxide (NO) resulted in elevated blood pressure and its effect on resistance arteries, rats were offered NG-nitro-L-arginine methyl ester (L-NAME), a competitive inhibitor of NO synthase, in their drinking water. Blood pressure (BP) rose slightly from 100 +/- 2 mmHg in controls to 130 +/- 5 mmHg with 25 mg/Kg L-NAME per day and to 173 +/- 9 mmHg with 100 mg/Kg per day for 2 1/2 to 4 weeks. Rats were studied after 1-2 weeks of hypertension (BP > 150 mmHg). The concentration of cyclic guanosine monophosphate, the intracellular second messenger of NO, was significantly depressed in aorta and in the mesenteric vascular bed in L-NAME-treated rats. Mesenteric resistance arteries studied on a wire-myograph exhibited similar external and lumen diameters, whereas media width and media/lumen ratio were greater (p < 0.01). Cross-sectional area of the media was similar. Active wall tension in response to norepinephrine tended to be greater in blood vessels from L-NAME-treated rats, while responses to vasopressin and endothelin-1 were unaltered. Sensitivity to norepinephrine was significantly enhanced in L-NAME-treated rats (p < 0.001), while that to endothelin-1 and arginine8 vasopressin was similar. In conclusion, administration of an NO synthase inhibitor produces hypertension, with exaggerated media/lumen ratio in resistance arteries and enhancement of response to norepinephrine, which together with decreased NO generation may contribute to elevation of blood pressure.
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PMID:Effect of hypertension induced by nitric oxide synthase inhibition on structure and function of resistance arteries in the rat. 768 50

We investigated the effect of nitric oxide, derived from L-arginine on the production of endothelin-1 in vivo and in cultured endothelial cells. In mechanically ventilated anesthetized dogs (n = 5), mean pulmonary arterial pressure (mPAP), pulmonary vascular resistance (PVR) and plasma endothelin-1 level of the femoral artery during hypoxic ventilation (FIO2 = 0.10) were 3.3 +/- 0.4kPa, 68.7 +/- 10.2kPa.s-1/L and 47.2 +/- 17.4ng/L respectively. NG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased the peak value of mPAP and PVR during hypoxic ventilation to 4.9 +/- 0.6 kPa and 160.9 +/- 34.6kPa. s/L and its effect lasted for 3 hours. Meanwhile, plasma endothelin-1 level in the femoral artery was increased to 68.2 +/- 20.6, 72.8 +/- 20.9, 75.8 +/- 22.7 ng/L at 60, 120, 180 minutes respectively after the injection of L-NAME (P < 0.05 vs hypoxic control before the injection). In cultured endothelial cells from human umbilical veins, endothelin-1 level of culture medium increased significantly in 10(-11) and 10(-7) mol/L L-NAME group (n = 9, P < 0.05 vs control group). These findings indicate that endogenous nitric oxide is an inhibitory modulator of hypoxic pulmonary vasoconstriction and that nitric oxide inhibits the production of endothelin-1 in vivo and in cultured vascular endothelial cells.
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PMID:[Effect of NG-nitro-L-arginine methylester on the secretion of endothelin-1 in vivo and in cultured endothelial cells]. 778 Aug 24

The interaction between endothelin-1 (ET-1) (5 pmol/mouse, i.c.v.) and endothelin-3 (ET-3) (5 pmol/mouse, i.c.v.) with NG-nitro-L-arginine methyl ester (L-NAME) (5 mg/kg i.p., 30 min pretreatment) was investigated in mice by the use of two experimental procedures: hot plate and tail flick tests in mice. L-NAME showed slight insignificant antinociceptive action, but augmented significantly the antinociceptive effects of i.c.v. administered ET-1 and ET-3 in both experimental tests.
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PMID:L-NAME augments the antinociceptive effects of intracerebroventricularly applied ET-1 and ET-3. 783 29

The aim of this study is to investigate the effects of nitric oxide, formed from L-arginine, on the production of endothelin-1 in vivo and in cultured endothelial cells. In mechanically ventilated anesthetized dogs (n = 5), mean pulmonary arterial pressure (PAPm) and pulmonary vascular resistance (PVR) during hypoxic ventilation (FIO2 = 0.10) was 25 +/- 3.1 kPa and 68.7 +/- 10.2 kPa.s/L respectively. NG-nitro-L-arginine methylester (L-NAME), an inhibitor of nitric oxide synthase, increased the peak value of PAPm and PVR during hypoxic ventilation to 36.6 +/- 4.7 kPa and 158.4 +/- 25 kPa.s/L and its effect lasted for 2-3 hours. Meanwhile, plasma endothelin-1 level in the femoral artery increased by 20.9 +/- 7.1, 25.6 +/- 7.7, 28.6 +/- 7.9 pg/ml at the 60th, 120th, 180th minute after the injection of L-NAME respectively (P < 0.05 vs hypoxic control before the injection). In cultured endothelial cells from umbilical veins, endothelin-1 level of culture medium in control group was 35.1 +/- 5.9 pg/10(5) cells/ml (n = 9). L-NAME increased endothelin-1 level to 42.8 +/- 4.9pg/10(5) cells/ml (n = 9, P < 0.05) in case of 10(-11) mol/L and to 43.0 +/- 4.7 pg/10(5) cells/ml in case of 10(-7) mol/L (n = 9, P < 0.05). These findings indicate that endogenous nitric oxide is an inhibitory modulator of hypoxic pulmonary vasoconstriction and that nitric oxide inhibits the production of endothelin-1 in vivo and in cultured vascular endothelial cells.
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PMID:Inhibition of nitric oxide synthesis increases the secretion of endothelin-1 in vivo and in cultured endothelial cells. 786 88

To determine the influences of both PO2 and the presence of the endothelium on contractile responses of the human umbilical artery (HUA), the effects of a series of vasoconstrictors were compared in ring preparations with and without endothelium at low (2.5% O2, PO2 < 55 mmHg (1 mmHg = 133.3 Pa)) and high PO2 (95% O2, PO2 > 600 mmHg). The results demonstrate the following. (i) 5-Hydroxytryptamine (5-HT) and endothelin-1 (ET-1) contracted the HUA at either low or high PO2. At low PO2, removal of the endothelium significantly reduced receptor-mediated responses. (ii) The nitric oxide synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME, 100 microM) did not modulate 5-HT-initiated contractions at either level of PO2. (iii) alpha-Methyl-5-hydroxytryptamine (alpha-Me-5-HT) and 5-carboxamidotryptamine (5-CT), relatively selective 5-HT1C/5-HT2 and 5-HT1-like receptor agonists, respectively, elicited contractions in the HUA, and the responses were reduced at low PO2 but unaffected by removal of the endothelium. (iv) Responses of the HUA to high potassium (hK+) were unaffected by either changes in PO2 or removal of the endothelium. (v) The 5-HT2 receptor antagonist ketanserin at low concentration (10 nM) inhibited contractile responses to 5-HT in an apparently competitive manner. However, with 100 nM ketanserin and at low PO2, inhibition became noncompetitive. Removal of the endothelium did not influence the action of ketanserin. (vi) Regardless of PO2, the Ca2+ channel antagonist nifedipine (1 microM) significantly inhibited 5-HT- and ET-1-mediated contractions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The endothelium contributes to the contractile responses of the human umbilical artery to 5-hydroxytryptamine and endothelin-1 under low but not high PO2 conditions. 788 82

1. The present study characterizes the receptors responsible for endothelin-1-induced release of thromboxane A2 from the guinea pig lung and of endothelium-derived nitric oxide from the rabbit perfused kidney, by the use of the selective ETA receptor antagonist, BQ-123, and a novel selective ETB receptor antagonist, BQ-788. 2. In the guinea pig perfused lung, endothelin-1 (ET-1) (5 nM) induced a marked increase of thromboxane A2 which was reduced by 17 +/- 5.0, 70 +/- 1.0 and 93 +/- 1.2% by BQ-788 infused at concentrations of 1, 5 and 10 nM respectively. In contrast, BQ-123 (0.1 and 1.0 microM) had little or no effect on the ET-1-induced release of thromboxane A2. 3. In the same perfused model, the selective ETB agonist, IRL 1620 (50 nM), stimulated the release of thromboxane A2, but not prostacyclin. The eicosanoid-releasing properties of IRL 1620 were abolished by BQ-788 at 10 nM, yet were unaffected by BQ-123 (1 microM). 4. In the rabbit perfused kidney, BQ-788 (10 nM) potentiated the increase of perfusion pressure induced by endothelin-1 (1, 5 and 10 nM) by approximately 90%, but not that induced by angiotensin II (1 microM). Furthermore, the selective ETB receptor antagonist did not reduce the release of prostacyclin triggered by either peptide. 5. In another series of experiments, pretreatment of the perfused kidney with a nitric oxide synthase inhibitor, L-NAME (100 microM), potentiated the pressor responses to both endothelin-1 and angiotensin II. Under L-NAME treatment, BQ-788 did not further potentiate the pressor response to endothelin-1. 6 Our results illustrate the predominant role of ETB receptor activation in the release of thromboxane A2 and nitric oxide triggered by endothelin-l in the guinea pig perfused lung and rabbit kidney respectively.
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PMID:Block of endothelin-1-induced release of thromboxane A2 from the guinea pig lung and nitric oxide from the rabbit kidney by a selective ETB receptor antagonist, BQ-788. 788 81

The effects of cooling on the isometric response of rabbit isolated central ear (cutaneous) and femoral (non-cutaneous) arteries to histamine were determined at 37 degrees C and 24 degrees C (cooling). Under resting tension, both types of arteries contracted to histamine (10(-7)-10(-3) M), and the sensitivity of ear arteries, but not of femoral arteries was lower at 24 than at 37 degrees C. Chlorpheniramine (10(-7) M) blocked the contraction of both types of arteries to histamine at both temperatures. In ear arteries, endothelium removal or treatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME, 10(-5) M) did not affect the contraction to histamine at 37 degrees C, but it reversed the decreased contraction at 24 degrees C. In femoral arteries, endothelium removal or L-NAME (10(-5) M) did not affect the response to histamine at 37 and 24 degrees C. Ear and femoral arteries precontracted with endothelin-1 (10(-8)-10(-7) M) and pretreated with chlorpheniramine (10(-5) M) relaxed to histamine (10(-7)-10(-4) M), and the sensitivity of this relaxation in ear arteries, but not in femoral arteries, increased at 24 degrees C. The relaxation of ear and femoral arteries to histamine was not modified by endothelium removal, L-NAME (10(-5) M) or meclofenamate (10(-5) M), but it was blocked by cimetidine (10(-6) M) at 37 degrees C and 24 degrees C. These results suggest: (1) ear and femoral arteries have contracting H1 and relaxing H2 receptors, probably located on smooth musculature, and (2) cooling reduces the contraction and increases the relaxation of cutaneous arteries to histamine: the reduction of this contraction could be caused by an augmented availability of endothelial nitric oxide, and the increment of this relaxation could be caused by an augmented sensitivity of H2 receptors of smooth musculature induced by cooling. These features do not seem to occur in deep vessels.
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PMID:Cooling effects on the histaminergic response of rabbit ear and femoral arteries: role of the endothelium. 797 17

Calcitonin gene-related peptide (CGRP) is a novel polypeptide that exerts important effect on the cardiovascular system through its vasorelaxant properties. We studied in vivo in normal rats the effect of acute administration of CGRP on whole kidney function and showed that the intravenous infusion of the peptide resulted in a fall of blood pressure associated with a marked increase in renal plasma flow (RPF) as well as glomerular filtration rate (GFR). These changes were reversible with discontinuation of CGRP infusion. To evaluate whether the renal hemodynamic responses to the peptide were mediated by endogenous vasodilatory prostaglandins of endothelial origin, animals were preexposed to indomethacin, a cyclooxygenase enzyme inhibitor. Inhibition of prostaglandins synthesis with indomethacin failed, however, to prevent the increase in RPF and GFR observed during CGRP infusion. By contrast, NG-nitro-L-arginine methyl ester (L-NAME), which inhibits the synthesis of nitric oxide, a newly discovered endothelium-derived relaxing factor, completely abolished the renal hemodynamic changes induced by CGRP. Moreover, L-arginine infusion in L-NAME-treated rats restored the renal response to CGRP. We have also shown that systemic infusion of CGRP progressively normalized RPF and GFR that were reduced in response to a bolus intravenous injection of the vasoconstrictor endothelin-1. This indicates that CGRP regulates renal hemodynamics and modulates the deleterious effects of vasoconstrictive substances on the kidney.
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PMID:Calcitonin gene-related peptide reduces renal vascular resistance and modulates ET-1-induced vasoconstriction. 797 88

1. We assessed regional haemodynamic responses to the vasodilator, MgSO4, in the absence and presence of the nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME), in conscious chronically instrumented Long Evans rats (n = 9). 2. MgSO4 (loading dose 220 mumol kg-1 min-1 for 7 min, maintenance dose 56 mumol kg-1 min-1 for 7 min), alone, caused slight bradycardia and hypotension accompanied by reductions in renal and mesenteric flows, but a marked hyperaemic vasodilatation in the hindquarters (flow, delta 54 +/- 6%, vascular conductance, delta 77 +/- 5%). 3. L-NAME (183 nmol kg-1 min-1) caused hypertension (29 +/- 2 mmHg) accompanied by bradycardia (-51 +/- 6 beats min-1) and reductions in flow and vascular conductance in the renal (-18 +/- 4% and -35 +/- 3%, respectively), mesenteric (-35 +/- 3% and -49 +/- 3%, respectively), and hindquarters (-26 +/- 3% and -42 +/- 3%, respectively) vascular beds. In the presence of L-NAME, the hypotensive and bradycardic effects of MgSO4 were still apparent, but its hindquarters hyperaemic vasodilator effect was significantly attenuated. 4. In order to determine if the inhibitory action of L-NAME on the hindquarters hyperaemic vasodilator action of MgSO4 was a non-specific effect, due to the change in baseline conditions caused by L-NAME, we also examined responses to MgSO4 in the presence of endothelin-1 (12.5 pmol kg-1 min-1) or angiotensin II (50 pmol kg-1 min-1). In the presence of either peptide, the overall effects of MgSO4 on hindquarters flow and vascular conductance were unchanged. 5. In a separate experiment (n = 8) we determined that the inhibitory effect of L-NAME on the hyperaemic vasodilator response to MgSO4 was prevented by L-arginine, and also demonstrated that the Beta2-adrenoceptor antagonist, ICI 118551, caused significant inhibition of the hindquarters haemodynamic effects of MgSO4.6. We conclude that the hindquarters haemodynamic effects of MgSO4 in conscious rats involve a substantial L-NAME-sensitive component which depends on activation of Beta2-adrenoceptors, probably asa consequence of adrenal medullary adrenaline release.
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PMID:Effects of NG-nitro-L-arginine methyl ester on regional haemodynamic responses to MgSO4 in conscious rats. 801 14


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