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Query: UMLS:C0406810 (
NAME
)
13,345
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Inhibition of the angiotensin converting enzyme (ACE) with ramipril was studied in male Wistar rats during long-term inhibition of nitric oxide (NO) synthase by NG-nitro-L-arginine methyl ester (L-
NAME
). Chronic treatment with L-
NAME
in a dose of 25 mg/kg per day over 6 weeks caused myocardial hypertrophy and a significant increase in systolic blood pressure (245 +/- 16 mmHg) as compared to controls (155 +/- 4 mmHg). Animals receiving simultaneously L-
NAME
and ramipril were protected against blood pressure increase and partially against myocardial hypertrophy. L-
NAME
caused a significant reduction in glomerular filtration rate (
GFR
: 2.56 +/- 0.73 ml.kg-1.min-1) and renal plasma flow (RPF: 6.93 +/- 1.70 ml.kg-1.min-1) as compared to control (
GFR
: 7.29 +/- 0.69, RPF: 21.36 +/- 2.33 ml.kg-1.min-1). Addition of ramipril prevented L-
NAME
-induced reduction in
GFR
and renal plasma flow. L-
NAME
produced an elevation in urinary protein excretion and serum creatinine and a decrease in potassium excretion which was antagonised by ramipril. L-
NAME
-induced increase in plasma renin activity (PRA) was further elevated with ramipril treatment. Isolated hearts from rats treated with L-
NAME
showed increased post-ischaemic reperfusion injuries. Compared to controls duration of ventricular fibrillation was increased and coronary flow reduced. During ischemia the cytosolic enzymes lactate dehydrogenase and creatine kinase, as well as lactate in the venous effluent were increased. Myocardial tissue values of glycogen, ATP, and creatine phosphate were decreased, whereas lactate was increased.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Ramipril prevents the detrimental sequels of chronic NO synthase inhibition in rats: hypertension, cardiac hypertrophy and renal insufficiency. 753 99
Because the kidneys are vasodilated and the endogenous production of nitric oxide is increased in gravid rats, we tested whether nitric oxide mediates the renal vasodilatory response to pregnancy. Chronically instrumented, conscious rats of gestational days 12-14 were studied concurrently with age-matched virgin control animals.
GFR
and effective renal plasma flow (ERPF) were determined by the renal clearances of inulin and para-aminohippurate before and during acute infusion of N omega-nitro-L-arginine methyl ester (
NAME
; 2, 20, and 50 micrograms/min) or NG-monomethyl-L-arginine (100 micrograms/min). Baseline
GFR
and ERPF were significantly increased, and effective renal vascular resistance was decreased by 30-40% in gravid rats compared with virgin controls. During infusion of all three dosages of
NAME
and NG-monomethyl-L-arginine, effective renal vascular resistance,
GFR
, and ERPF were equalized in the pregnant and virgin rats (the only exception being
GFR
during the 20 micrograms/min
NAME
infusion). When compared with virgin rats, the gravid animals were more responsive to nitric oxide synthase inhibition, showing a significantly greater decline in
GFR
and ERPF and rise in effective renal vascular resistance at each timepoint during the infusion of inhibitor. To exclude the possibility that nonspecific renal vasoconstriction per se led to equalization of renal function in the two groups of rats, we investigated angiotensin II. In contrast to the results observed with nitric oxide synthase inhibitors, pregnant rats were less responsive to the renal vasoconstrictory effects of angiotensin II, such that the baseline differences in renal parameters measured before infusion of the hormone were increased during the infusion. To determine whether nitric oxide synthase was inhibited to a similar extent in gravid and virgin rats, aortic and renal cortical cGMP content was assayed ex vivo at the end of inhibitor infusion. The lower 2-micrograms/min dose of
NAME
consistently reduced cGMP content of these tissues to comparable levels in the two groups of rats. In conclusion, we suggest that nitric oxide mediates reduced renal vascular resistance and hyperfiltration during pregnancy in conscious rats.
...
PMID:Acute blockade of nitric oxide synthase inhibits renal vasodilation and hyperfiltration during pregnancy in chronically instrumented conscious rats. 754 83
Acute nitric oxide blockade not only potentiates the vasoconstrictor actions of endothelin but also enhances the synthesis and release of endothelin. To investigate whether the vasoconstrictor actions of acute nitric oxide blockade are modulated by endothelin, studies were conducted in the conscious, chronically catheterized rat. Renal function was measured before and during acute nitric oxide blockade with nitro-L-arginine methylester (L-
NAME
), L-
NAME
+ endothelin blockade with the endothelin-converting enzyme inhibitor phosphoramidon, or L-
NAME
+ the nonpeptide ETA and ETB receptor antagonist Bosentan. The increases in blood pressure and RVR seen with acute nitric oxide blockade were attenuated by either method of concomitant endothelin blockade. The falls in RPF and
GFR
were not blunted because endothelin blockade produced parallel reductions of both pressor and renal vasoconstrictor responses to acute nitric oxide blockade. Endothelin blockade alone with either endothelin-converting enzyme inhibitor or the nonpeptide ETA and ETB receptor antagonist had little effect on blood pressure, RPF, or RVR, but increases in urinary sodium excretion and a small decline in
GFR
were observed with Bosentan. These observations indicate that endogenous endothelin exerts a tonic antinatriuretic action in the normal conscious rat and partially mediates the pressor actions of acute nitric oxide blockade.
...
PMID:Endothelin modulates the pressor actions of acute systemic nitric oxide blockade. 858 26
Cyclosporine (CsA) administration and nitric oxide (NO) blockade promote similar chronic renal hemodynamic alterations in rats. We evaluated various clinical CsA doses under conditions of NO blockade using L-
NAME
(N-nitro L-arginine methyl ester). Groups of Sprague-Dawley rats kept on a normal salt (+NaCl) or low-salt (-NaCl) diet were given CsA 7.5 mg/kg, 2.5 mg/kg, or vehicle (VH) for 21 days. CsA or VH treatment was preceded by one week of L-
NAME
and continued for three weeks. Inulin clearance, CsA blood level, and weekly blood pressure change were assessed at 28 days. Marked CsA dose dependent reductions in
GFR
in -NaCl animals (P < 0.01 versus VH + L-
NAME
) and +NaCl animals (P < 0.05 versus VH + L-
NAME
, +NaCl) as well as blood pressure elevations (P < 0.01 versus VH + L-
NAME
at 28 days) occurred in groups concurrently treated with CsA and L-
NAME
. In addition, Impaired renal function and morphologic lesions in rats (CsA 2.5 mg/kg) receiving L-
NAME
or CsA alone demonstrated CsA blood levels within the therapeutic range of human renal transplant patients. VH groups treated with L-
NAME
alone produced blood pressure elevations but were spared of renal functional or morphological alterations. Primary renal morphologic lesions in CsA treated animals included proximal tubule collapse and vacuolization and, less frequently, interstitial edema and vacuolization of interstitial cells. Unique to rats treated simultaneously with CsA and L-
NAME
were vascular abnormalities consisting of endothelial and arteriolar medial hyperplasia and occasional acute medial necrosis. In conclusion, acute CsA nephrotoxicity can be enhanced by simultaneous NO blockade, suggesting NO has a protective effect in CsA-induced nephropathy. These results can be achieved with a drug exposure profile that correlates with clinical therapy.
...
PMID:Clinically relevant doses and blood levels produce experimental cyclosporine nephrotoxicity when combined with nitric oxide inhibition. 863 80
The current study was performed in 30 anesthetized and mechanically ventilated newborn rabbits to investigate the role of the endothelium-derived relaxing factor nitric oxide (NO) in the renal vasoconstriction observed during hypoxemia. Renal blood flow (RBF) and
GFR
were determined by the clearance of p-aminohippuric acid and inulin, respectively. In nine newborn rabbits (group 1), acute hypoxemia induced a significant decrease in RBF (-17 +/- 7%) and
GFR
(-11 +/- 6%). A second group of nine animals was used to determine the role of NO in regulating renal hemodynamics of the immature kidney in physiologic conditions. N omega-Nitro-L-arginine methyl ester (L-
NAME
), a NO synthesis inhibitor, significantly increased the renal vascular resistance by 31 +/- 9% and decreased RBF and
GFR
(-20 +/- 6% and -13 +/- 5%, respectively). Acute hypoxemia was induced in 12 additional newborn rabbits during L-
NAME
infusion (group 3) to define the role of NO in the renal vasoconstriction observed during hypoxemia. The changes in renal hemodynamics were greater in this group than in those induced by hypoxemia alone. The present results suggest that: 1) endogenous NO has a crucial role in maintaining basal renal perfusion, 2) the activity of NO synthase is maintained during acute hypoxemia, and 3) NO could blunt the effects of acute hypoxemia in the immature newborn rabbit kidney.
...
PMID:Role of nitric oxide in the hypoxemia-induced renal dysfunction of the newborn rabbit. 884 51
We investigated the effect of euvolemic surgical preparation, on chemical indices of activity of the nitric oxide (NO) system, in anesthetized, acutely prepared rats. The urinary excretion of NO2+NO3 (UNOXV) and cGMP (UcGMPV) increased progressively during the experiment. Pretreatment with aminoguanidine or dexamethasone, inhibitors of inducible NO synthase (iNOS), prevented the increase in UNOXV and UcGMPV but had no impact on mean arterial pressure (BP), renal vascular resistance (RVR) or
GFR
. Since these variables did not change in the conscious rat, the increased UNOXV results from some aspect of the acute surgical preparation. When acutely prepared rats received L-
NAME
, a non-specific NOS inhibitor, BP and RVR increased but paradoxical increases in UNOXV and UcGMPV were also seen. Nonselective NOS inhibition (+L-
NAME
) was fatal in 50% of acutely prepared rats, causing cardiac contracture. The same dose of L-
NAME
produced no deaths in either conscious chronically catheterized rats or in acutely prepared rats, previously subjected to sterile surgery and acute L-
NAME
in the conscious state. These data indicate that acute, nonsterile surgery induces expression of iNOS, but that the additional NO generated has no obvious cardiovascular/renal actions. Acute UNOXV and UcGMPV do not predict total NO production, or "hemodynamically active" NO. Generalized NO inhibition in rats acutely stressed by surgery/anesthesia can be fatal.
...
PMID:Impact of surgery on nitric oxide in rats: evidence for activation of inducible nitric oxide synthase. 918 87
Excess NO generation plays a major role in the hypotension and systemic vasodilatation characteristic of sepsis. Yet the kidney response to sepsis is characterized by vasoconstriction resulting in renal dysfunction. We have examined the roles of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) on the renal effects of lipopolysaccharide administration by comparing the effects of specific iNOS inhibition, -N6-(1-iminoethyl)lysine (L-NIL), and 2,4-diamino6-hydroxy-pyrimidine vs. nonspecific NOS inhibitors (nitro- -arginine-methylester). cGMP responses to carbamylcholine (CCh) (stimulated, basal) and sodium nitroprusside in isolated glomeruli were used as indices of eNOS and guanylate cyclase (GC) activity, respectively. LPS significantly decreased blood pressure and
GFR
(112+/-4 vs. 83+/-4 mmHg; 2.66+/-0.29 vs. 0. 96+/-0.22 ml/min, P < 0.05) and inhibited the cGMP response to CCh. GC activity was reciprocally increased. L-NIL and 2, 4-diamino-6-hydroxy-pyrimidine administration prevented the decrease in
GFR
(2.71+/-0.28 and 3.16+/-0.18 ml/min, respectively), restored the normal response to CCh, and GC activity was normalized. In vitro application of L-NIL also restored CCh responses in LPS glomeruli. Neuronal NOS inhibitors verified that CCh responses reflected eNOS activity. L-
NAME
, a nonspecific inhibitor, worsened
GFR
(0.41+/-0.15 ml/min), a reduction that was functional and not related to glomerular thrombosis, and eliminated the CCh response. No differences were observed in eNOS mRNA expression among the experimental groups. Selective iNOS inhibition prevents reductions in
GFR
, whereas nonselective inhibition of NOS further decreases
GFR
. These findings suggest that the decrease in
GFR
after LPS is due to local inhibition of eNOS by iNOS, possibly via NO autoinhibition.
...
PMID:Inhibition of constitutive nitric oxide synthase (NOS) by nitric oxide generated by inducible NOS after lipopolysaccharide administration provokes renal dysfunction in rats. 921 22
To evaluate therapeutic options for the prevention of radiocontrast media (RCM)-induced nephropathy, a model was developed in which rats received NG-nitro-L-arginine methyl ester (L-
NAME
) for 10 wk in order to inhibit nitric oxide (NO) synthetase. This study tests the hypothesis that infusion of an adenosine antagonist before RCM application may avoid the vasoconstrictive response in NO-depleted rats. Rats received L-
NAME
for 10 wk orally (50 mg/L drinking water) to achieve NO depletion. Renal function was determined by [3H]inulin clearance for analysis of the
GFR
and by flowmetry for assessing renal blood flow (RBF). After a control clearance period (baseline clearance period), the renal response to RCM application (sodium diatrizoate, 2 ml/kg body wt) was measured two times every 30 min starting 30 min after RCM application (clearance periods 1 and 2). L-
NAME
rats and control rats received two adenosine antagonists. The nonselective adenosine antagonist theophylline was given as an initial bolus of 50 mumol/kg body wt within 10 min, followed by continuous infusion of 100 mumol/kg body wt per h, and the specific adenosine A1-receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) was given as a bolus of 100 micrograms/kg body wt before RCM application. Results were compared with vehicle infusion. In the control group, no significant change of
GFR
or RBF could be detected after application of RCM with or without prior infusion of DPCPX or theophylline. In L-
NAME
rats, RBF decreased significantly after RCM application (baseline, 5.6 +/- 0.2 ml/min; first clearance period, 4.6 +/- 0.3 ml/min [P < 0.05]; second clearance period, 4.3 +/- 0.3 [P < 0.01]).
GFR
was also reduced in L-
NAME
rats without previous infusion of theophylline or DPCPX (baseline, 0.95 +/- 0.1 ml/min; first clearance period, 0.83 +/- 0.1 ml/min; second clearance period, 0.69 +/- 0.1 ml/min [P = 0.058]). Prior treatment with either theophylline or DPCPX resulted in complete protection against a decline of RBF and
GFR
induced by RCM in L-
NAME
rats. Rats with chronic NO blockade showed a significant increase of the renal vasoconstrictive effect of contrast media. Application of L-
NAME
in rats seems to constitute a suitable animal model to study the pathophysiology of radiocontrast media-induced nephropathy. In this animal model, administration of adenosine antagonists prevented the decline of
GFR
and RBF.
...
PMID:Prevention of radiocontrast-induced nephropathy by adenosine antagonists in rats with chronic nitric oxide deficiency. 921 62
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.
...
PMID:Angiotensin II blockade does not prevent renal effects of L-NAME in sodium-repleted humans. 932 81
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.
...
PMID:Dopamine-2 receptor blockade potentiates the renal effects of nitric oxide inhibition in humans. 945 16
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