Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In seven healthy, young subjects on a 240 mmol sodium diet, mean arterial pressure (MAP), renal hemodynamics, and renal handling of Na and exogenous Li were measured at baseline and during short-term nitric oxide (NO) blockade with a 90-minute infusion of 3.0 microg x kg(-1) x min(-1) of N(G)-L-arginine methyl ester (L-NAME). The infusion was performed twice: after a 3-day pretreatment with either placebo or 50 mg losartan to block Ang II receptors. With placebo, L-NAME produced no change in MAP from 0 to 45 minutes (period 1) and only a 5% increase at 45 to 90 minutes (period 2) of infusion. Effective renal plasma flow (ERPF, PAH clearance) and glomerular filtration rate (GFR, inulin clearance) declined by 11.7% and 8.0%, respectively in period 1 and by 14.6% and 11.6%, respectively, in period 2. Calculated renal vascular resistance (RVR) increased by 13.0% to 20.6%. Fractional excretion of Na (FE(Na)) and Li (FE(Li)) fell by 30.0% and 21.0%, respectively, in period 1 and by 44.2% and 31.1% in period 2. All these variations were significant versus baseline. With losartan, the rise in MAP at 45 to 90 minutes was completely abolished, whereas all changes in ERPF, GFR, RVR, FE(Na), and FE(Li) in response to L-NAME were the same as those observed with placebo. The present data show that NO blockade with low-dose systemic infusion of L-NAME produces renal vasoconstriction, reduced GFR, and increased tubular Na reabsorption independent of changes in MAP. Reduced FE(Li) indicates an effect of NO on the proximal tubule. Since these changes are not prevented by losartan, we conclude that in Na-repleted humans, renal vasoconstriction and Na-retaining effects of inhibition of basal NO production are not due to the unopposed action of endogenous Ang II.
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PMID:Angiotensin II blockade does not prevent renal effects of L-NAME in sodium-repleted humans. 932 81

Inhibition of nitric oxide (NO) synthesis by structural analogues of L-arginine reduces glomerular filtration, renal blood flow, sodium excretion, and urine output. N(G)-nitro-L-arginine methyl ester (L-NAME) inhibits constitutive and inducible isoforms of NO synthase, while aminoguanidine (AG) selectively inhibits inducible isoforms of NO synthase. We assessed the NO-inhibitory activity of AG on renal function. Rats were treated with aminoguanidine 50 mg/kg daily for 2 months, followed by L-NAME (25 mg/kg/day) for 1 week to inhibit all NO synthase isoforms. After treatment with L-NAME, we performed baseline renal function measurements, then infused L-arginine (2.5 mg/100 g BW x min) to reverse NO inhibition and assessed whether AG exerted NO-inhibitory activity independently of L-NAME. Prior to L-arginine infusion, AG-treated rats did not differ from controls with respect to body weight, kidney weight, systolic blood pressure, urine flow rate, urinary protein or albumin excretion, or urinary excretion of NO metabolites. After L-arginine infusion, all animals showed a 10-15% decrease in mean arterial blood pressure. L-Arginine-induced increases in urine flow, inulin clearance, PAH clearance, sodium excretion, and NO metabolite excretion were blunted in aminoguanidine-treated animals. To assess long-term effects of aminoguanidine, rats were treated for 12 months. Urinary excretion of NO metabolites was lower than controls. Inulin clearance was higher than controls. Aminoguanidine blunts the effect of L-ariginine on renal hemodynamics independently of the nitric oxide synthase inhibitor, L-NAME. However, the use of aminoguanidine for 12 months in rats did not adversely affect renal function.
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PMID:Nitric oxide-inhibitory effect of aminoguanidine on renal function in rats. 939 25

In eight young healthy subjects on a 240 mM Na diet mean arterial pressure (MAP), renal hemodynamics and renal handling of Na and exogenous Li were measured at baseline and during acute nitric oxide (NO) inhibition with 90-minute infusion of 3.0 microg/kg x min(-1) of N(G)-L-arginine methyl ester (L-NAME). The same experiment was repeated with infusion of 50 microg/kg x min(-1) of DA2 receptor blocker L-Sulpiride (L-SULP) alone and, finally, with simultaneous infusion of both L-NAME and L-SULP. L-SULP alone did not elicit any effect. L-NAME alone produced no changes in MAP from 0 to 45 minutes (P1) and a 6.6% increase at 45 to 90 minutes (P2) of infusion. Effective renal plasma flow (ERPF, PAH clearance) and glomerular filtration rate (GFR, inulin clearance) declined by 10.2% and 7.6%, respectively, in P1 and by 15.3% and 11.5% in P2. Filtration Fraction (FF) rose by 4.2% in P2. Calculated renal vascular resistance (RVR) increased by 13.0% to 25.6%. Fractional excretion of Na (FENa) and Li (FELi) fell by 20.0% and by 16.0%, respectively, in P1 and by 40.0% and 25.1% in P2. All these variations, except for MAP and GFR, were significantly greater during coinfusion of L-NAME and L-SULP. ERPF declined by 17.8% to 33.7%, FENa by 26.7% to 53.3%, FELi by 13.8% to 34.8%, while RVR rose by 22.5% to 59.1% and FF by 10.1% to 29.3%. The present data confirm that NO blockade with low-dose systemic infusion of L-NAME produces renal vasoconstriction, reduced GFR with slight increase in FF, and enhanced tubular Li, and Na reabsorption. Since increase in RVR and FF and decrease in FENa and FELi are markedly potentiated by the simultaneous infusion of DA2 blocker L-SULP, which exerts no effects by itself, we suggest that DA interactions between DA system at the level of DA2 receptors and basal NO production play a physiological role in the regulation of renal function in humans.
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PMID:Dopamine-2 receptor blockade potentiates the renal effects of nitric oxide inhibition in humans. 945 16

Both short-term and long-term nitric oxide (NO) blockade were shown to cause an increase in O(2)(-) activity. To assess the contribution of such enhanced O(2)(-) activity in the kidney, responses to administration of the NO synthase inhibitor nitro-L-arginine methyl ester (L-NAME; 200 microg.min(-1).kg body wt(-1)) were assessed in knockout mice the lacking NAD(P)H oxidase subunit gp91(phox) (KO; n = 10) and in wild-type (WT; n = 10) mice. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearances, respectively. Baseline RBF was higher in KO compared with WT mice (5.8 +/- 0.5 vs. 4.5 +/- 0.3 ml.min(-1).g(-1); P < 0.04) without significant differences in GFR (0.62 +/- 0.04 vs. 0.73 +/- 0.05 ml.min(-1).g(-1)) and in mean arterial pressure (MAP; 91 +/- 6 vs. 88 +/- 4 mmHg). L-NAME infusion for 60 min caused similar increases in MAP (114 +/- 6 vs. 113 +/- 3 mmHg) in both groups but resulted in a lesser degree of reduction in RBF in KO compared with WT mice (-7 +/- 3 vs. -17 +/- 3%; P < 0.02), although GFR remained unchanged in both groups. The natriuretic response to systemic L-NAME infusion was attenuated in KO compared with WT mice (Delta: 3.1 +/- 0.7 vs. 5.2 +/- 0.6 micromol.min(-1).g(-1)). L-NAME increased urinary 8-isoprostane excretion rate in WT (5.9 +/- 1 to 7.7 +/- 1 pg.min(-1).g(-1); P < 0.02) but not in KO mice (5.6 +/- 1 to 4.9 +/- 0.3 pg.min(-1).g(-1)). In contrast, responses to another vasoconstrictor, norepinephrine, were similar in both strains of mice. These data indicate that activation of NAD(P)H oxidase results in the enhancement of O(2)(-) activity that influences renal hemodynamics and excretory function in the condition of NO deficiency.
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PMID:Reduced renal responses to nitric oxide synthase inhibition in mice lacking the gene for gp91phox subunit of NAD(P)H oxidase. 1859 78

Peroxynitrite (ONOO(-)) is formed endogenously by the reaction of nitric oxide (NO) and superoxide (O(2)(-)). To examine the hypothesis that OONO(-) cause renal vasodilation at low concentrations but cause vasoconstriction at higher concentrations, we examined renal responses to intra-arterial infusion of incremental doses of OONO(-) (10, 20, and 40 microg.kg(-1).min(-1); 45 min each) in anesthetized rats. Renal blood flow (RBF) and glomerular filtration rate (GFR) were determined by PAH and inulin clearance. In control rats (n = 6), low dose (10 microg.kg(-1).min(-1)) of OONO(-) increased RBF by 10 +/- 3% and GFR by 15 +/- 5%. The higher doses (20 and 40 microg.kg(-1).min(-1)) mostly reversed these responses which were -7 +/- 4 and -27 +/- 7% (P < 0.05) in RBF and -0.1 +/- 4.8 and -14 +/- 12% in GFR, respectively. There were no appreciable changes in urine flow (V) and sodium excretion (U(Na)V) during OONO(-) infusion. However, in rats pretreated with NO synthase (NOS) inhibitor, l-NAME (50 microg.kg(-1).min(-1); n = 5), these doses of ONOO(-) significantly reduced RBF (-26 +/- 7, -27 +/- 6, and -44 +/- 3%) and GFR (-21 +/- 6, -25 +/- 8, and -32 +/- 12%) with variable increases in V or U(Na)V. Long-term infusion of OONO(-) (10 microg.kg(-1).min(-1) for 75 min) in another set of control rats (n = 5) also showed similar vasodilator and hyperfiltration responses. These data indicate that ONOO(-) acts as an oxidant at high concentration but provides renoprotective function at low concentration that depends on intact NOS activity.
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PMID:Renal hemodynamic and excretory responses to intra-arterial infusion of peroxynitrite in anesthetized rats. 1898 12