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

Age-related renal functional changes may relate to alterations in the responsiveness to vasoconstrictors and vasodilators. Blood pressure and renal responses to angiotensin II (ANG II), endothelin-1 (ET), NG-nitro-L-arginine methyl ester (L-NAME), and to the ANG II receptor antagonist losartan were compared in young (3-mo-old) and older (15-mo-old) male rats. Baseline mean arterial pressure (MAP) values were slightly lower in the older rats, and glomerular filtration rate (GFR) and renal plasma flow (RPF) were higher. ANG II and ET induced comparable pressor responses in both groups but produced greater GFR and RPF reductions in the older rats. In contrast, the MAP, GFR, and RPF responses to L-NAME were exaggerated in aging rats. Losartan induced modest MAP reductions in both groups, and comparable renal vasodilatory responses. Thus the aging kidney exhibits exaggerated responses to systemic vasoconstrictor stimuli, whereas responsiveness to ANG II blockade is preserved but not enhanced. Whether or not this balance is further impaired later in the aging process remains to be determined.
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PMID:Altered renal vascular responses in the aging rat kidney. 802 73

1. The role of endothelial dysfunction in the gastric microcirculatory responses during local endothelin-1 (ET-1) infusion has been investigated in the pentobarbitone-anaesthetized rat. Furthermore, the involvement of prostanoids or nitric oxide (NO) in these actions has been investigated by the use of indomethacin to inhibit cyclo-oxygenase and NG-nitro-L-arginine methyl ester (L-NAME) to inhibit NO synthase. 2. Close-arterial infusion of ET-1 (1-10 pmol kg-1 min-1 for 10 min) induced a dose-dependent increase in the gastric leakage of radiolabelled albumin, used as an index of endothelial cell dysfunction. 3. Close-arterial infusion of a submaximal dose of ET-1 (5 pmol kg-1 min-1 for 10 min) significantly increased gastric albumin leakage after 2 min infusion, which reached maximal levels after 10 min, and only slowly declined during the 30 min observation period. 4. By contrast, gastric blood flow, as assessed by laser Doppler flowmetry, did not significantly increase until after 5 min of infusion of ET-1 (5 pmol kg-1 min-1 for 10 min), reaching a maximum after 17 min, and was sustained for the 30 min observation period. 5. Pretreatment with L-NAME (2 mg kg-1, i.v.) or indomethacin (5 mg kg-1, i.v.) significantly reduced both the hyperaemic response to ET-1 and the increase in gastric albumin leakage, and in combination abolished these responses. 6. These results suggest that locally released NO and prostanoids mediate the gastric vasodilator response to close arterial infusion of ET-1. This hyperaemia is preceded by changes in gastric albumin extravasation and hence may be initiated as a response to direct endothelial injury by ET-1.
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PMID:The involvement of endothelial dysfunction, nitric oxide and prostanoids in the rat gastric microcirculatory responses to endothelin-1. 803 49

The objective of the present study was to evaluate if endothelin plays a role in the maintenance of arterial blood pressure in normotensive guinea pigs. For this purpose, the effects of a new mixed (ETA + ETB) endothelin receptor antagonist, Ro 47-0203 (bosentan), were evaluated in vitro on aortic rings and in anesthetized and conscious guinea pigs. In vitro, bosentan was a potent (pA2 = 7.5) and competitive endothelin receptor antagonist as shown by the parallel rightward shift of the concentration-response curve for endothelin-1 on guinea pig aortic rings in presence of increasing concentrations of bosentan. In vivo, bosentan significantly decreased arterial blood pressure of both anesthetized and conscious guinea pigs. This effect was similar to the effect of BQ-123, a selective ETA receptor antagonist. No additional effect was observed when bosentan was given on top of BQ-123. Neither inhibition of the renin angiotensin system with remikiren, cyclooxygenase inhibition with indomethacin, bradykinin antagonism with Hoe 140, ganglionic blockade with chlorisondamine, parasympathetic inhibition with atropine nor nitric oxide synthase blockade with L-NAME altered the effect of bosentan. In conclusion, the present results show that endothelin contributes to the maintenance of arterial blood pressure in normal normotensive guinea pigs most likely through stimulation of ETA receptors.
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PMID:Endothelin plays a role in the maintenance of blood pressure in normotensive guinea pigs. 803 62

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

Renal vasoconstrictor responses to the adenosine A1 agonist N6-cyclopentyladenosine (CPA) were compared in the in situ autoperfused rat kidney to responses evoked by angiotensin II (ANG II), endothelin-1 (ET-1), arginine vasopressin (AVP), carbocyclic thromboxane A2 (CTxA2), phenylephrine (PE), and 5-hydroxytryptamine (5-HT). On the basis of their ED50 values (dose of agonist, in mass units, that produced 50% of maximal response to that agonist), the order of vasoconstrictor potency was ANG II > or = AVP > ET-1 > CPA > 5-HT > or = PE > CTxA2. Dose-response curves to CPA were shallower and maximal responses were weaker than those produced by the other agonists. Maximal responses, the log ED50, and the slope of the dose-response curve to CPA were markedly potentiated in the presence of the nitric oxide (NO) synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Selective antagonism of A1 receptors increased renal blood flow and markedly attenuated CPA-induced renal vasoconstriction in the absence or presence of L-NAME but had no effect on the maximal responses to ANG II. Conversely, AT1 receptor antagonism attenuated renal vasoconstriction produced by ANG II but had little effect on the produced by CPA. These results suggest that endogenous NO modulates renal vasoconstriction produced by A1 receptor stimulation and provide evidence against an interaction between renovascular adenosine A1 and angiotensin AT1 receptors.
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PMID:Interactions of adenosine A1 receptor-mediated renal vasoconstriction with endogenous nitric oxide and ANG II. 823 45

1. The objectives of the present experiments were to assess the role of endogenous nitric oxide (NO) in mediating and/or modulating the effects of endothelin-1 (ET-1) on blood pressure and microvascular permeability in conscious rats. 2. Intravenous administration of the NO synthesis inhibitors, NG-monomethyl-L-arginine (L-NMMA) or NG-nitro-L-arginine methyl ester (L-NAME) at a dose (25 mg kg-1 or 2 mg kg-1, respectively) which evoked maximum increase in mean arterial blood pressure (MABP) significantly attenuated (by about 40%) the vasodepressor response and potentiated (by 100-180%) the pressor response to ET-1 (1 nmol kg-1, i.v.) compared to the effects of ET-1 in animals where the peripheral vasoconstrictor effects of L-arginine analogues were mimicked by an infusion of noradrenaline (620-820 ng kg-1 min-1). Similar inhibition of the depressor and potentiation of the pressor actions of ET-1 were observed when the MABP which had been elevated by L-NMMA or L-NAME was titrated to normotensive levels with hydralazine or diazoxide before injection of ET-1. 3. L-NAME (2 mg kg-1) increased the vascular permeability of the large airways, stomach, duodenum, pancreas, liver, kidney and spleen (up to 280%) as measured by the extravasation of Evans blue dye. The permeability of pulmonary parenchyma, skeletal muscle and skin was not affected significantly by L-NAME treatment. Elevation of MABP by noradrenaline infusion did not evoke protein extravasation in the vascular beds studied with the exception of the lung. In the large airways, tissue Evans blue content was similar following noradrenaline infusion and L-NAME.4. Both the pressor and permeability effects of L-NAME (2 mg kg-1) were effectively reversed by L-arginine (300 mg kg- 1) but not by D-arginine (300 mg kg-1 ). The D-enantiomer of L-NAME, D-NAME(2 mg kg-1) had no effect on the parameters studied.5. Protein extravasation was significantly enhanced by ET-1 (1 nmol kg-1) in the upper and lower bronchi, stomach, duodenum, kidney and spleen (up to 285%). This was potentiated by L-NAME(2 mg kg-1), resulting in marked increases in tissue Evans blue accumulation (up to 550%) in these tissues. The effects of L-NAME and ET-1 were additive in the trachea, duodenum, pancreas and liver.Combined administration of L-NAME plus ET-1 significantly increased protein extravasation in the pulmonary parenchyma, where neither L-NAME nor ET-1 alone caused significant increases.6. Noradrenaline infusion (620-820 ng kg-1 min-1) potentiated the permeability action of ET-1(1 nmol kg-1) in the pulmonary circulation, whereas it did not modify ET-1-induced protein extravasation in the other vascular beds.7. These results indicate that endogenous NO mediates, in part, the vasodepressor effect and attenuates the vasopressor action of ET-1 and modulates the effects of ET-1 on vascular permeability. These findings confirm the role of NO in the maintenance of blood pressure and suggest an important role for NO in the regulation of microvascular permeability.
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PMID:Vascular responses to endothelin-1 following inhibition of nitric oxide synthesis in the conscious rat. 829 11

Intravenous infusion of endothelin-1 (ET-1) in the cat, 60 pmol x kg body wt-1 x min-1 for 5 min, induced an increase in mean arterial blood pressure (MAP) of 41.3 +/- 4.8 mmHg (n = 6; P < 0.001). Blood flow, as determined with radioactive microspheres, was reduced in many tissues. Reductions by 70-80% were observed in the choroid plexus, pineal and pituitary glands. Total cerebral blood flow was reduced by 18-23%. Pre-treatment with indomethacin or a combination of indomethacin and L-NAME caused vasoconstriction in many tissues and modified the responses to ET-1 in a variable way, suggesting that normally, ET-1 tends to release arachidonic acid metabolites and nitric oxide with great variations between different tissues. Intracerebroventricular infusion (i.c.v.) of ET-1, 10 pmol x kg body wt-1 x min-1, caused an increase in MAP of 79 +/- 11 mmHg (n = 6; P < 0.001). Regional blood flow in the medulla oblongata, medulla spinalis, choroid plexus, pineal and pituitary glands was reduced by 60-80%. Heart rate, cardiac output and coronary blood flow were significantly increased after 30 min i.c.v. infusion, indicating an activation of the heart, most probably as part of a central ischaemic response. Our results indicate that in many tissues the vasoconstrictive effect of ET-1 is influenced by indomethacin- and L-NAME-sensitive vasodilator mechanisms that are activated by the peptide. In the CNS, there may be marked effects on regional blood flow after i.c.v. infusion.
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PMID:Vascular effects of endothelin-1 in the cat; modification by indomethacin and L-NAME. 835 28

Endothelium-derived nitric oxide (EDNO) is an important vasodilator substance produced by the vascular endothelium. The present in vivo and in vitro study is aimed at evaluating its role in vascular regulation and its interactions with norepinephrine (NE), endothelin-1 (ET) and superoxide anion. In male anesthetized wistar rats, inhibition of the in vivo EDNO pathway with L-NAME (an established specific inhibitor of EDNO synthesis, 1-4 (mg/kg, iv bolus) provoked sustained, dose-dependent hypertensive responses (mean arterial pressure increased 45 +/- 1.5% over baseline for more than 60 minutes at a dose of 4 mg/kg, mean +/- Sx, which was completely reversed by L-arginine, the normal substrate for EDNO synthesis). In the in vitro study on rat aortic rings, blocking the endothelial production of EDNO with L-NAME (10(-4) M), caused the most prominent enhancement of the contractile responses to NE (increased maximal responses and lowered EC50), a smaller enhancement of contraction to ET and minimal modification of the vasoconstrictive effects of superoxide anion. L-arginine (10(-4) M), on the contrary, slightly attenuated the contraction to NE and ET but without the contraction to superoxide anion. The present study confirms that EDNO system represents one of the most important physiological depressor mechanisms in vivo, and indicates that EDNO is an important, differential antagonistic mechanism against the vasoconstrictors. It is also demonstrated that L-arginine availability is generally not the rate-limiting step in the in vivo generation of EDNO. The implications of the results were discussed.
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PMID:Endothelium-derived nitric oxide: role in vascular regulation and interaction with norepinephrine, endothelin and superoxide anion. 839 68

This study investigates the vasodilatory effects of endothelin-1 (ET-1) in isolated guinea pig aortic rings in vitro. Cumulative dose-response curves to ET-1 were constructed and ET-1 actions on prostaglandin F2 alpha (PGF2 alpha)-precontraction were studied in both endothelium-intact and endothelium-denuded preparations, in the presence or absence of a cyclooxygenase inhibitor (indomethacin) and/or nitric oxide inhibitors (NG-nitro-L-arginine methyl ester and hemoglobin). In endothelium-intact preparations, pretreatment with indomethacin (10(-5) M, 30 min), alone or in combination with NG-nitro-L-arginine methyl ester (L-NAME, 10(-4) M), significantly augmented the constrictive responses to ET-1, whereas indomethacin, L-NAME, and hemoglobin (10(-5) M) had no significant effects in the endothelium-denuded preparations. Furthermore, in PGF2 alpha-precontracted, endothelium-intact preparations, ET-1, at a dose of 10(-9) M, induced initial relaxation followed by subsequent contraction, while it only contracted the endothelium-denuded preparations. The initial relaxation was abolished by indomethacin, but not by L-NAME or hemoglobin. In addition, this relaxation was not inhibited by a specific ETA receptor antagonist, BQ-123 (6 x 10(-6) M). In addition to the involvement of nitric oxide, these results show the involvement of cyclo-oxygenase-generated vasodilating eicosanoid(s) derived from endothelium in ET-1-induced vasorelaxation in guinea pig aorta in vitro. The results also indicate that this vasorelaxation is mediated by ETB receptor activation.
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PMID:Involvement of cyclo-oxygenase-generated vasodilating eicosanoid(s) in addition to nitric oxide in endothelin-1-induced endothelium-dependent vasorelaxation in guinea pig aorta. 840 21

1. The objective of the present study was to assess whether inhibition of nitric oxide (NO) production could modulate vascular permeability in the coronary circulation in conscious rats. 2. Intravenous injection of NG-nitro-L-arginine methyl ester (L-NAME, 2 mg kg-1) resulted in a slowly developing hypertension and evoked twofold increases in vascular permeability in the left ventricle and right atrium as measured by the extravasation of Evans blue dye. Maintenance of mean arterial blood pressure at the level observed following L-NAME injection by infusion of noradrenaline (620-820 ng kg-1 min-1) did not induce significant protein extravasation in the coronary circulation. 3. L-NAME treatment markedly enhanced (up to 490%) protein extravasation both in the left ventricle and right atrium in response to platelet-activating factor (PAF, 1.9 nmol kg-1, i.v.) and endothelin-1 (1 nmol kg-1, i.v.). Noradrenaline infusion potentiated (up to 69%) endothelin-1-induced protein extravasation. The permeability effect of PAF was only slightly enhanced by noradrenaline. 4. The present findings indicate that inhibition of endogenous NO synthesis leads to an increase in protein extravasation and to potentiation of the permeability effects of PAF and endothelin-1 in the coronary circulation. These results also suggest that NO may be an important regulator of vascular permeability under physiological and pathological conditions.
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PMID:Nitric oxide modulates vascular permeability in the rat coronary circulation. 844 83


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