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

Four chronic experiments were performed to assess changes in the activity and gene expression of type I nitric oxide synthase (NOS) at the macula densa (MD) and of renin expression and immunoreactivity (IR) at the juxtaglomerular apparatus (JGA) of rat kidney, as follows: 1) two-kidney, one-clip Goldblatt hypertension (2K1C, for 3 and 40 days; sham operation for controls), 2) furosemide treatment (150 mg/kg-1.day-1 ip for 5 days), 3) chronic low-salt diet (0.02%) vs. high-salt diet (3%; both for 11 days), and 4) chronic blockade of NOS by nitro-L-arginine methyl ester (L-NAME, 40 mg.kg-1.day-1 for 2 mo). NOS and renin gene expression, NOS enzyme activity and renin IR were semiquantitatively evaluated with histochemical methods (NADPH diaphorase, in situ hybridization, immunohistochemistry). In 2K1C, marked increases were induced in NOS and renin in the ischemic vs. contralateral kidneys both after 3 and 40 days, respectively (P < 0.05). Related to controls, significant increases in the ischemic kidney were encountered after 3 and 40 days, whereas contralateral suppression of NOS and renin was found only after 40 days. Furosemide treatment resulted in a marked increase of both NOS and renin levels compared with controls (P < 0.05). Salt restriction induced a significant elevation of NOS levels compared with salt loading (P < 0.05), whereas only minor changes were evident in renin levels. L-NAME treatment resulted in a moderate reduction of NOS activity (not significant), whereas renin levels were markedly reduced (P < 0.05). These results show that NOS activity and gene expression are inversely related to chronic changes in renal perfusion, salt balance, and salt transport at the distal tubule in parallel with the known response of renin to these changes. Inhibition of NOS decreases renin levels at the JGA. The histochemical findings support previous concepts that MD-derived NO is involved in the control of renin synthesis.
 ...
PMID:Parallel regulation of constitutive NO synthase and renin at JGA of rat kidney under various stimuli. 859 73

This study sought to examine the involvement of prostaglandins and of nitric oxide (NO) in the macula densa-dependent activation of the renin system in vivo. For this purpose, male Sprague-Dawley rats were chronically infused with furosemide (12 mg/day) for 6 days to inhibit macula densa salt transport. To inhibit the synthesis of prostaglandins and of NO, animals were injected with indomethacin (2 mg/kg twice daily) and with nitro-L-arginine methyl ester (L-NAME; 40 mg/kg twice daily) for the last 2 days of the experiment, respectively. Furosemide infusion increased plasma renin activity (PRA) from 8.8 +/- 1.4 to 41 +/- 5.2 ng angiotensin I (ANG I).h-1.ml-1 and renin mRNA levels from 112 +/- 8 of standard to 249 +/- 18% of standard. After treatment with indomethacin, the furosemide-induced increases in renin mRNA levels was attenuated to 190 +/- 11% of standard. After injections of L-NAME, both the furosemide-induced increases of renin mRNA levels and of PRA were reduced to 126 +/- 14% of standard and 22 +/- 5 ng ANG I.h-1.ml-1, respectively. These findings suggest that activation of renin gene expression by blockade of the macula densa function is dependent on intact NO and prostaglandin formation, whereas for stimulation of renin secretion mainly intact NO formation appears to be necessary.
 ...
PMID:Nitric oxide and prostaglandins are involved in the macula densa control of the renin system. 859 76

Nitric oxide (NO) is produced by and relaxes pulmonary arteries and veins; however, a role for NO as a participant in the control of pulmonary vascular resistance (PVR) remains to be defined. Here we investigated the hypothesis that for NO to serve as a determinant of PVR in the rabbit requires the presence of blood. In isolated blood-perfused rabbit lungs, NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) increased PVR and the slope of the pressure-flow relationship. These effects of L-NAME were prevented by pretreatment with L-arginine. In contrast, in lungs perfused with a physiological salt solution, L-NAME had no effect on PVR or the pressure-flow relationship. The addition of washed red blood cells (RBCs) to physiological salt solution, but not the addition of plasma and platelets, restored the response to L-NAME. This effect of RBCs was not reproduced by increasing perfusate viscosity with dextran. These results suggest that, in the rabbit lung, NO is a determinant of PVR in the presence of blood. Moreover, that aspect of blood that permits the generation of NO appears to be related to the RBC and not to perfusate viscosity.
 ...
PMID:Effect of L-NAME on pressure-flow relationships in isolated rabbit lungs: role of red blood cells. 859 2

Long-term nitric oxide blockade by N omega -nitro-L-arginine methyl ester (L-NAME) leads to severe and progressive hypertension. The role of salt intake in this model is unclear. To verify whether salt dependence in this model is related to the extent of nitric oxide inhibition, we gave adult male Munich-Wistar rats a low salt, standard salt, or high salt diet and oral L-NAME treatment at either 3 or 25 mg/kg per day. At 10 to 15 days of treatment, the slope of the pressure-natriuresis line was decreased in rats receiving low-dose L-NAME compared with untreated controls. In rats treated with the higher dose, the line was shifted to the right but remained parallel to that obtained in untreated controls. Renal vascular resistance was moderately increased in rats receiving low-dose L-NAME, whereas high-dose L-NAME induced a marked vasoconstriction that was aggravated by salt overload. Low-dose L-NAME treatment induced hypertension only when associated with sodium overload. In rats receiving high-dose L-NAME, hypertension was aggravated by sodium excess but was not ameliorated by sodium restriction. Long-term (6 weeks) L-NAME treatment was associated with progressive hypertension, which was aggravated by salt overload, and with the development of albuminuria, focal glomerular collapse, glomerulosclerosis, and renal interstitial expansion. These abnormalities were worsened by salt overload and largely prevented by salt restriction. In the model of chronic nitric oxide blockade, salt dependence is a function of the inhibitor dose, and renal injury varies directly with the level of salt intake.
 ...
PMID:Effect of salt intake and inhibitor dose on arterial hypertension and renal injury induced by chronic nitric oxide blockade. 862 Dec 12

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

1. The aims of this study were to compare in the rat isolated perfused lung preparation, the dilator actions of nicorandil, pinacidil and nitroglycerin on the hypoxic pulmonary pressure response with or without hypercapnic acidosis and to investigate the possible involvement of K channels and EDRF in these effects. 2. Isolated lungs from male Wistar rats (260-320 g) were ventilated with 21%O2 + 5%CO2 + 74%N2 (normoxia) or 5%CO2 + 95%N2 (hypoxia) and perfused with a salt solution supplemented with ficoll and gassed with 40%CO2 + 60%N2 to produce hypercapnic acidosis. Glibenclamide (1 microM), charybdotoxin (0.1 microM), NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) and methylene blue (30 microM) were used to block KATP channels, KCa channels, EDRF synthesis and guanylate cyclase, respectively. 3. Hypoxic pressure response was significantly increased by hypercapnic acidosis (+115%, P < 0.001), L-NAME (+111%, P < 0.001), methylene blue (+100%, P < 0.05) but not by glibenclamide or charybdotoxin. In contrast none of these inhibitors affected the hypoxic hypercapnic acidosis response. 4. Nicorandil, pinacidil and nitroglycerin caused relaxation during the hypoxic pressure response and hypoxic hypercapnic acidosis response. Nicorandil was more potent in the latter. Glibenclamide inhibited the relaxant effects of nicorandil and pinacidil but not those of nitroglycerin during hypoxia alone. In contrast, glibenclamide inhibited the relaxant effects of the three drugs during hypoxia + hypercapnia. Charybdotoxin inhibited the relaxant effect of pinacidil during normocapnia and hypoxia but not those of nicorandil or nitroglycerin. Methylene blue inhibited partially the dilator response to pinacidil but did not modify the effects of nitroglycerin or nicorandil. 5. It is concluded that in the rat isolated lung preparation, EDRF limits hypoxic pulmonary vasoconstriction but not hypoxic vasoconstriction potentiated by hypercapnic acidosis, whereas KATP or KCa channels are not involved in either case. Nicorandil and pinacidil dilate pulmonary vessels mainly through KATP channels but the effects of pinacidil may also involve an additional mechanism of action through KCa channels. Finally it is suggested that nitroglycerin may partly exert its relaxant effects through KATP channels.
 ...
PMID:Comparison of the effects of nicorandil, pinacidil and nitroglycerin on hypoxic and hypercapnic pulmonary vasoconstriction in the isolated perfused lung of rat. 864 7

This study aimed to investigate the possible involvement of endothelial autacoids such as nitric oxide or prostaglandins in the well-known stimulatory effect of a low salt intake on renin secretion and renin gene expression in the kidney. To this end, plasma renin activity (PRA) and kidney renin mRNA levels were determined in male Sprague-Dawley rats fed either a normal (0.6% w/w) or a low (0.03%) NaCl diet for 10 days. To inhibit nitric oxide formation, the animals received L-nitro-argininemethylester (L-NAME, 40 mg/ kg twice a day), to inhibit prostaglandin formation the animals received meclofenamate (8 mg/kg twice a day) during the last 2 days. In animals fed a normal salt diet, L-NAME decreased PRA from 6.5 to 4.9 ng angiotensin I x h(-1) x ml(-1) and decreased renin mRNA levels by about 15%. Meclofenamate did not change PRA or renin mRNA in animals fed on normal salt diet. In vehicle-treated animals fed a low salt diet, PRA increased from 6.5 to 20.2 ng ANGI x h(-1) x ml(-1) and renin mRNA levels increased by 100%. Meclofenamate treatment did not alter these changes of PRA and renin mRNA during the intake of a low salt diet. In animals treated with L-NAME, PRA increased to only 7.2 ng ANGI x h(-1) x ml(-1) and renin mRNA increased by 20%. These findings indicate that inhibition of nitric oxide formation but not of prostaglandin formation substantially attenuates the stimulatory effect of a low salt intake on the renin system, suggesting that nitric oxide is required for this process.
 ...
PMID:Blockade of nitric oxide formation inhibits the stimulation of the renin system by a low salt intake. 866 93

1. The effects of the sodium salt of the weak acid lactate on tension and intracellular pH (pH1) were studied in rat mesenteric small arteries mounted on a wire myograph. Sodium lactate was substituted iso-osmotically for sodium chloride. 2. At a concentration of 50 mM, both L- and D-stereoisomers of lactate markedly relaxed arteries preconstricted with noradrenaline (NA) within 10 min. The concentration-response relationship for L-lactate showed that the NA contracture was relaxed by 50% at approximately 26 mM. L-Lactate did not, however, relax arteries preconstricted with high-K+(45 mM) solution. 3. L-Lactate did not alter extracellular pH (pHo) but caused a small but significant decrease in pH1, measured using the pH-sensitive fluorochrome, 2',7'-bis(carboxyethyl)-5-(6)-carboxyfluorescein (BCECF). Relaxation to L-lactate was unaffected when this change in pHi was offset by the simultaneous addition of NH4Cl to the solution. 4. Sodium pyruvate (50 mM) caused a significant intracellular acidosis but did not relax arteries preconstricted with NA. 5. L-Lactate-induced relaxations were unaffected by removal of the endothelium or when the synthesis of nitric oxide (NO) was inhibited by 10(-4) M N omega-nitro-L-arginine methyl ester (L-NAME). 6. The potassium channel blockers glibenclamide (10 microM), 4-aminopyridine (3 mM) and tetraethylammonium chloride (10 mM) did not affect L-lactate-induced relaxation in arteries preconstricted with NA. Inhibition of guanylate cyclase with Methylene Blue, or cyclooxgenase with indomethacin, also did not affect relaxation to L-lactate. 7. The Rp stereoisomer of adenosine-3',5'-cyclic monophosphothioate (Rp-cAMPS), an analogue of cAMP which inhibits competitively stimulation of protein kinase A, reduced significantly L-lactate-induced relaxation at a concentration of 25 microM. Rp-cAMPS also significantly reduced forskolin-induced relaxation of the NA contracture. 8. It is concluded that L-lactate-induced relaxation in this vascular bed is pHi-1 endothelium-, and nitric oxide-independent. It is not mediated by inhibition of voltage-gated Ca2+ channels, opening of K+ channels, prostacylin or cyclic GMP. cAMP may however play a role in L-lactate-induced relaxation.
 ...
PMID:Mechanism of lactate-induced relaxation of isolated rat mesenteric resistance arteries. 868 76

The purpose of this study was to dissociate effects of reduced viscosity from those of low arterial O2 content (CaO2) on cerebral blood flow (CBF) during anemia. Three groups (n = 8) of pentobarbital sodium-anesthetized cats were studied: 1) a time-control group with a hematocrit of 32 +/- 1% (SE), 2) an anemia group that underwent an isovolumic exchange transfusion with albumin in a salt solution to decrease hematocrit to 18 +/- 1%, and 3) a group transfused with cell-free, tetramerically stabilized hemoglobin to decrease hematocrit equivalently to that in the albumin-transfused group. CaO2 (in ml/dl) in the hemoglobin-transfused group (11.8 +/- 0.3) and the control group (15.0 +/- 0.6) was greater than that in the albumin group (8.7 +/- 0.3). CBF (in ml.min-1.100 g-1) in the hemoglobin group (45 +/- 3) and control group (36 +/- 4) was less than that in the albumin group (60 +/- 3). Consequently, cerebral O2 transport (CaO2 x CBF) was similar in the hemoglobin, control, and albumin groups (5.3 +/- 0.3, 5.3 +/- 0.4, and 5.2 +/- 0.2 ml.min-1.100 g-1, respectively). After infusion of N omega-nitro-L-arginine methyl ester (L-NAME) to inhibit nitric oxide (NO) synthase, CBF in the hemoglobin group remained lower than that in the albumin group, suggesting that NO scavenging by hemoglobin did not solely account for the lower CBF. In contrast, the neurohypophysis (posterior pituitary) exhibited substantial decreases in blood flow that were not augmented by L-NAME administration after hemoglobin transfusion and that were similar in magnitude to L-NAME alone. Thus NO scavenging by cell-free hemoglobin may be more prominent in high-flow, protein-permeable regions enriched with NO synthase. These results support the hypothesis that O2 transport to cerebrum is well regulated when CaO2 is manipulated independently of hematocrit and viscosity.
 ...
PMID:Cerebral O2 transport with hematocrit reduced by cross-linked hemoglobin transfusion. 877 20

The pulmonary vascular responses to changes in perfusate viscosity were studied in isolated rat lungs treated with the nitric oxide synthase (NOS) inhibitors, N omega-nitro-L-arginine methyl ester (L-NAME) and N omega- monomethyl-L-arginine (L-NMMA). Lungs were isolated according to standard protocols and perfused with varying concentrations of albumin in physiological salt solution (PSS) and with low, intermediate, and normal hematocrits using washed erythrocytes. Pressure-flow curves were generated by increasing pulmonary arterial pressure (PPA) while keeping pulmonary venous pressure (PPV) constant and measuring flow at each pressure interval. Neither perfusate flow nor pulmonary vascular resistance changed after L-NAME or L-NMMA (300 microM) at any pressure interval in lungs perfused with 4 and 10% albumin/PSS. In lungs perfused with 20% albumin/PSS, L-NMMA decreased flow at all PPA tested except 10 cm H2O (P < 0.05). L-NAME decreased flow in lungs perfused with normal (39.2 +/- 2.1%) hematocrits at all PPA tested. Conversely, L-NAME decreased flow in lungs perfused with low and intermediate hematocrits only at the highest pressure intervals. L-Arginine, when given after NOS inhibitors, failed to restore flow to baseline values in any group of lungs. N omega-nitro-D-arginine methyl ester (300 microM) did not change flow at any pressure interval in lungs perfused with normal (43 +/- 1.5%) hematocrit, washed erythrocytes. We conclude that lungs perfused with intermediate and normal hematocrit, washed erythrocytes, as well as with high-viscosity albumin/PSS solutions, show increased pulmonary vascular responses to NOS inhibitors.
 ...
PMID:Perfusate viscosity and hematocrit determine pulmonary vascular responsiveness to NO synthase inhibitors. 892 83


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>