The Central Effects of a Nitric Oxide Synthase Inhibitor (Nω- Nitro - L - Arginine) on Blood Pressure and Plasma Renin

1993 ◽  
Vol 15 (5) ◽  
pp. 819-832 ◽  
Author(s):  
Abbas O. El karib ◽  
Jiangjun Sheng ◽  
A. Lorris Betz ◽  
Richard L. Malvin
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Plasma Renin ◽  
Nitric Oxide Synthase Inhibitor ◽  
Central Effects ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Nitric Oxide in Streptozotocin-Induced Diabetes Mellitus in Rats

1996 ◽  
Vol 90 (5) ◽  
pp. 379-384 ◽  
Author(s):  
Abed Maree ◽  
Gari Peer ◽  
Adrian Iaina ◽  
Miriam Blum ◽  
Yoram Wollman ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Body Weight ◽  
Nitric Oxide Synthase ◽  
Creatinine Clearance ◽  
Diabetic Rats ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Oxide Synthase

1. The present study was performed to determine the relationship between diabetic glomerular hyperfiltration and nitic oxide as modulated by the chronic administration of l-arginine and/or N-ω-nitro-l-arginine, a known nitric oxide synthase inhibitor in streptozotocin-induced diabetic rats. 2. Normal rats and rats drinking hypertonic glucose (10%) were used as time-controlled groups. Six weeks after administration of streptozotocin the diabetic rats had significantly higher creatinine clearance (667 ± 53 μl min−1 100 g−1 body weight) than before and streptozotocin (456 ± 38 μl min−1 100 g−1 body weight, P<0.005) and very high plasma (37.8 ± 10.9 μmol/l) and urinary (3.492 ± 0.179 nmol min−1 100 g−1 body weight) nitrite + nitrate (stable metabolites of nitric oxide) values compared with before streptozotocin administration [19.3 ± 2.8 μmol/l (P<0.001) and 0.420 ± 0.051 nmol min−1 100 g−1 body weight (P<0.001) respectively]. The 6-week diabetic rats had higher systolic blood pressure (124.2 ± 2.9 mm Hg, P<0.05) than before streptozotocin (108 ± 8 mmHg), but had a value similar to that of the hypertonic-glucose-drinking rats. 3. The diabetic rats supplemented with l-arginine did not show an increase in creatinine clearance and had a lower urinary excretion of nitrite + nitrate (0.999 ± 0.27 nmol min−1 100 g−1 body weight, P<0.005) than the respective untreated streptozotocin-induced diabetic rats. Creatinine clearance increased in the normal and glucose-drinking rats that received l-arginine. The administration of l-arginine resulted in significant reduction in blood pressure in all groups studied. The chronic nitric oxide synthase inhibitor resulted in high blood pressure, and in a significant decrease in creatinine clearance and urinary nitrite + nitrate excretion in all groups studied. In both diabetic and glucose-drinking rats, the l-arginine therapy resulted in significantly lower plasma and urinary glucose levels than in their respective untreated control groups. 4. The nitric oxide synthase inhibitor increased the plasma and urinary glucose concentration in both diabetic and glucose-drinking rats. 5. Our results indicate that diabetic rats are characterized by high plasma concentrations and elevated urinary excretion of nitrite + nitrate, suggesting a state of high nitric oxide production. The vascular response to nitric oxide in diabetic rats may be different at the glomerular and peripheral vascular bed.

Upregulation of vascular inducible nitric oxide synthase mediates the hypotensive effect of ethanol in conscious female rats

2006 ◽  
Vol 100 (3) ◽  
pp. 1011-1018 ◽  
Author(s):  
Mahmoud M. El-Mas ◽  
Jian Zhang ◽  
Abdel A. Abdel-Rahman
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Hypotensive Effect ◽  
Female Rats ◽  
Hypotensive Action ◽  
Nitric Oxide Synthase Inhibitor ◽  
Synthase Inhibitor ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Previous reports from our laboratory have shown that ethanol elicits hypotension in female but not in male rats and that this effect of ethanol is estrogen dependent (El-Mass MM and Abdel-Rahman AA. Alcohol Clin Exp Res 23: 624–632, 1999; El-Mass MM and Abdel-Rahman AA. Clin Exp Hypertens 21: 1429–1445, 1999). In the present study, we tested the hypothesis that ethanol lowers blood pressure in female rats via upregulation of the inducible nitric oxide synthase (iNOS) in vascular tissues. The effects of pretreatment with NG-nitro-l-arginine (NOARG; nonselective nitric oxide synthase inhibitor) or aminoguanidine (selective iNOS inhibitor) on hemodynamic responses elicited by intragastric (ig) ethanol were determined in conscious female rats. Changes in vascular (aortic) iNOS protein expression evoked by ethanol in the presence and absence of aminoguanidine were also measured by immunohistochemistry. Compared with control (water treated) female rats, ethanol (1 g/kg ig) elicited hypotension that was associated with a significant increase in the aortic iNOS activity. The hypotensive effect of ethanol was virtually abolished in rats infused with the nitric oxide synthase inhibitor NOARG, suggesting a role for nitric oxide in ethanol hypotension. The inability of ethanol to lower blood pressure in NOARG-treated rats cannot be attributed to the presence of elevated blood pressure in these rats because ethanol produced hypotension when blood pressure was raised to comparable levels with phenylephrine infusion. Selective inhibition of iNOS by aminoguanidine (45 mg/kg ip), which had no effect on baseline blood pressure, abolished both the hypotensive action of subsequently administered ethanol and the associated increases in aortic iNOS content. These findings implicate vascular iNOS, at least partly, in the acute hypotensive action of ethanol in female rats.

Glomerular and tubular interactions between renal adrenergic activity and nitric oxide

1995 ◽  
Vol 268 (6) ◽  
pp. F1004-F1008 ◽  
Author(s):  
F. B. Gabbai ◽  
S. C. Thomson ◽  
O. Peterson ◽  
L. Wead ◽  
K. Malvey ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Glomerular Filtration ◽  
Renal Nerves ◽  
Ang Ii ◽  
Nitric Oxide Synthase Inhibitor ◽  
Adrenergic Activity ◽  
Single Nephron ◽  
Synthase Inhibitor ◽  
Oxide Synthase

Endothelium-dependent nitric oxide (EDNO) exerts control over the processes of glomerular filtration and tubular reabsorption. The importance of the renal nerves to the tonic influence of EDNO in the glomerular microcirculation and proximal tubule was tested by renal micropuncture in euvolemic adult male Munich-Wistar rats. The physical determinants of glomerular filtration and proximal reabsorption were assessed before and during administration of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA), in control animals and in animals 5–9 days after either ipsilateral surgical renal denervation (DNX) or after either sham surgery (SHX). L-NMMA caused single-nephron glomerular filtration rate to decline in control and SHX animals but not in DNX rats. L-NMMA caused a reduction in proximal reabsorption in control and SHX rats, which was prevented by prior DNX. DNX did not alter urinary guanosine 3',5'-cyclic monophosphate excretion, and, although DNX upregulates glomerular angiotensin II (ANG II) receptors, prior DNX did not alter intrarenal ANG II content as evaluated by radioimmunoassay. Some component of renal adrenergic activity is required for the full expression of the glomerular and tubular effects of blockade of nitric oxide synthase.

Effects of Early Neuronal and Delayed Inducible Nitric Oxide Synthase Blockade on Cardiovascular, Renal, and Hepatic Function in Ovine Sepsis

2010 ◽  
Vol 113 (6) ◽  
pp. 1376-1384 ◽  
Author(s):  
Matthias Lange ◽  
Atsumori Hamahata ◽  
Daniel L. Traber ◽  
Yoshimitsu Nakano ◽  
Aimalohi Esechie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Inducible Nitric Oxide Synthase ◽  
Nitric Oxide Synthase Inhibitor ◽  
Nitrite Nitrate ◽  
Synthase Inhibitor ◽  
Plasma Nitrite ◽  
Oxide Synthase ◽  
Organ Dysfunctions ◽  
Inducible Nitric Oxide

Background Recent evidence suggests that nitric oxide produced via the neuronal nitric oxide synthase is involved mainly in the early response to sepsis, whereas nitric oxide derived from the inducible nitric oxide synthase is responsible during the later phase. We hypothesized that early neuronal and delayed inducible nitric oxide synthase blockade attenuates multiple organ dysfunctions during sepsis. Methods Sheep were randomly allocated to sham-injured, nontreated animals (n = 6); injured (48 breaths of cotton smoke and instillation of Pseudomonas aeruginosa into the lungs), nontreated animals (n = 7); and injured animals treated with a neuronal nitric oxide synthase inhibitor from 1 to 12 h and an inducible nitric oxide synthase inhibitor from 12 to 24 h postinjury (n = 6). Results The injury induced arterial hypotension, vascular leakage, myocardial depression, and signs of renal and hepatic dysfunctions. The treatment significantly attenuated, but did not fully prevent, the decreases in mean arterial pressure and left ventricular stroke work index. Although the elevation of creatinine levels was partially prevented, the decreases in urine output and creatinine clearance were not affected. The injury-related increases in bilirubin levels, international normalized ratio, and lipid peroxidation in liver tissue were significantly attenuated. Although plasma nitrite/nitrate levels were significantly increased versus baseline from 12-24 h in controls, plasma nitrite/nitrate levels were not increased in treated animals. Conclusions The combination treatment shows potential benefit on sepsis-related arterial hypotension and surrogate parameters of organ dysfunctions in sheep. It may be crucial to identify the time course of expression and activation of different nitric oxide synthase isoforms in future investigations.

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