Renal and pressor effects of aminoguanidine in cirrhotic rats with ascites.

1996 ◽  
Vol 7 (12) ◽  
pp. 2694-2699
Author(s):  
M C Ortíz ◽  
L A Fortepiani ◽  
C Martínez ◽  
N M Atucha ◽  
J García-Estañ
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Liver Cirrhosis ◽  
Experimental Model ◽  
Systemic Blood Pressure ◽  
Arterial Hypotension ◽  
Control Group ◽  
No Production ◽  
Water Excretion ◽  
Excretory Function

Recent work indicates that nitric oxide (NO) plays an important role in the systemic and renal alterations of liver cirrhosis. This study used aminoguanidine (AG), a preferential inhibitor of inducible nitric oxide synthase (iNOS), to evaluate the role of this NOS isoform in the systemic and renal alterations of an experimental model of liver cirrhosis with ascites (carbon tetrachloride/ phenobarbital). Experiments have been performed in anesthetized cirrhotic rats and their respective control rats prepared for clearance studies. Administration of AG (10 to 100 mg/kg, iv) elevated dose-dependent mean arterial pressure (MAP, in mm Hg) in the cirrhotic rats from a basal level of 79.3 +/- 3.6 to 115.0 +/- 4.7, whereas in the control animals, MAP increased only with the highest dose of the inhibitor (from 121.8 +/- 3.6 to 133.3 +/- 1.4). In the cirrhotic group, AG also significantly increased sodium and water excretion, whereas these effects were very modest in the control group. Plasma concentration of nitrates+nitrites, measured as an index of NO production, were significantly increased in the cirrhotic animals in the basal period and decreased with AG to levels not significantly different from the control animals. Similar experiments performed with the nonspecific NOS inhibitor N omega-nitro-L-arginine (NNA) also demonstrated an increased pressor sensitivity of the cirrhotic rats, but the arterial hypotension was completely corrected. These results, in an experimental model of liver cirrhosis with ascites, show that AG exerts a beneficial effect as a result of inhibition of NO production, increasing blood pressure and improving the reduced excretory function. Because NNA, but not AG, completely normalized the arterial hypotension, it is suggested that the constitutive NOS isoform is also contributing in an important degree. It is concluded that the activation of both inducible and constitutive NOS isoforms plays an important role in the lower systemic blood pressure and associated abnormalities that characterize liver cirrhosis.

Effect of losartan on renal microvasculature during chronic inhibition of nitric oxide visualized by micro-CT

2003 ◽  
Vol 285 (5) ◽  
pp. F852-F860 ◽  
Author(s):  
Loudes A. Fortepiani ◽  
M. Clara Ortiz Ruiz ◽  
Federico Passardi ◽  
Michael D. Bentley ◽  
Joaquin Garcia-Estan ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Receptor Antagonist ◽  
Systemic Blood Pressure ◽  
No Synthase ◽  
Micro Ct ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Water Excretion ◽  
Renal Microvasculature

Chronic inhibition of nitric oxide (NO) synthase with the competitive l-arginine analog NG-nitro-l-arginine methyl ester (l-NAME) leads to an elevated systemic blood pressure and reduction in renal blood flow without significant changes in urinary sodium and water excretion. Simultaneous administration of ANG II AT1 receptor antagonist losartan and l-NAME prevents the alterations in blood pressure and renal hemodynamics. Microcomputed tomography (micro-CT) was used to investigate the role of ANG II in the changes of renal microvasculature during chronic NO inhibition. Sprague-Dawley rats were given l-NAME with or without AT1 receptor antagonist losartan (40 mg · kg-1 · day-1 each) in their drinking water for 19 days. Kidneys from each group (control, l-NAME-, and l-NAME + losartan-treated rats) were perfusion-fixed in situ, infused with a silicon-based polymer containing lead chromate, and scanned by micro-CT. The microvasculature in the reconstructed three-dimensional renal images was studied using computerized analytic techniques. Kidneys of l-NAME-treated rats had significantly fewer normal glomeruli (28,824 ± 838) than those of control rats (36,266 ± 3,572). Losartan normalized the number to control values (34,094 ± 1,536). The amount of vasculature in the cortex, outer medulla, and inner medulla of l-NAME-treated rats was about two-thirds that of control rats; losartan normalized the values to control levels. These data indicate that chronic treatment with the NO synthase inhibitor l-NAME produces a generalized rarefaction of renal capillaries. Because simultaneous AT1 receptor blockade abolished those changes, the data suggest that the reduction in vasculature is mediated by ANG II through AT1 receptors.

scholarly journals Factors Regulating Nitric Oxide Production in Spontaneously Hypertensive Rats Treated with Piper Sarmentosum Aqueous Extract

2020 ◽  
Vol 18 (3) ◽  
Author(s):  
Mohd Zainudin M ◽  
Elshami TFT ◽  
Ismawi HR ◽  
Hashim Fauzy F ◽  
Abdul Razak T
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Aqueous Extract ◽  
Antioxidant Activities ◽  
Control Group ◽  
No Production ◽  
Hypertensive Rats ◽  
Reducing Ability ◽  
Freeze Dried

Introduction: Hypertension is a major risk factor for cardiovascular diseases which is one of the leading causes of death worldwide. Piper sarmentosum (PS) has been widely used in traditional medicine with proven antihypertensive and antioxidant effects. This study aims to evaluate the antihypertensive potential of PS aqueous extract (PSAE) and to investigate the factors modulating nitric oxide (NO) production through its anti-oxidant activities. Methods: PS leaves were extracted with distilled water, freeze-dried and examined to quantify their antioxidant activities through 2,2-diphenyl-1-picrylhydrazyl and ferric reducing ability plasma test. The antihypertensive effect of PSAE in spontaneous hypertensive rats (SHR) was evaluated using four different groups (n=6); C (negative control), K (PSAE 500mg/kg), P (3 mg/kg perindopril) and M (PSAE 500 mg/kg + 1.5 mg/kg perindopril). PSAE and other treatments were given via oral gavage for 28 days. The blood pressure (BP) was determined using the non-invasive BP monitoring tail cuff technique and recorded weekly. SHR’s blood was collected to determine the serum NO level using Griess assay. Asymmetric dimethylarginine (ADMA) and arginine levels were determined using high performance liquid chromatography. Results: The extract showed good in-vitro antioxidant activities and a significant reduction in both systolic and diastolic BP compared to control group. They were also a decrease in plasma ADMA and an increase in serum NO level. Meanwhile, arginine level does not change significantly. Conclusion: High in-vitro antioxidant activities in PSAE enhances the clearance of ADMA that leads to an increase in serum NO production hence ameliorating the blood pressure of SHR.

Hemodynamic and renal effects of acute and progressive nitric oxide synthesis inhibition in anesthetized dogs

2001 ◽  
Vol 280 (1) ◽  
pp. R143-R148 ◽  
Author(s):  
Aleix Cases ◽  
John Haas ◽  
John C. Burnett ◽  
Juan Carlos Romero
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Methyl Ester ◽  
Ester Group ◽  
Pulmonary Vasculature ◽  
Control Group ◽  
No Production ◽  
Dependent Manner ◽  
Synthesis Inhibition ◽  
Anesthetized Dogs

This study evaluated the effects of progressive nitric oxide (NO) inhibition in the regulation of systemic and regional hemodynamics and renal function in anesthetized dogs. The N G-nitro-l-arginine methyl ester group ( n = 9) received progressive doses of 0.1, 1, 10, and 50 μg · kg−1 · min−1. Renal (RBF), mesenteric (MBF), iliac (IBF) blood flows, mean arterial pressure (MAP), pulmonary pressures, cardiac output (CO), and systemic and pulmonary vascular resistances were measured. During N G-nitro-l-arginine methyl ester infusion, MAP and systemic vascular resistances increased in a dose-dependent manner. Mean pulmonary pressure and pulmonary vascular resistances increased in both the N G-nitro-l-arginine methyl ester and the control group, but the increase was more marked in the N G-nitro-l-arginine methyl ester group during the last two infusion periods. CO decreased progressively, before any significant change in blood pressure was noticeable in the N G-nitro-l-arginine methyl ester group. IBF decreased significantly from the first N G-nitro-l-arginine methyl ester dose, whereas RBF and MBF only decreased significantly during the highest N G-nitro-l-arginine methyl ester dose. Urinary volume and sodium excretion only increased significantly in the time control group during the two last time periods. The pulmonary vasculature was more sensitive than the systemic vasculature, whereas skeletal muscle and renal vasculatures showed a greater sensitivity to the inhibition of NO production than the mesenteric vasculature. NO synthesis inhibition induces a progressive antidiuretic and antinatriuretic effect, which is partially offset by the increase in blood pressure.

Effects of NG-nitro-L-arginine methyl ester on renal function and blood pressure

1991 ◽  
Vol 261 (6) ◽  
pp. F1033-F1037 ◽  
Author(s):  
V. Lahera ◽  
M. G. Salom ◽  
F. Miranda-Guardiola ◽  
S. Moncada ◽  
J. C. Romero
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Renal Function ◽  
Methyl Ester ◽  
Renal Plasma Flow ◽  
Urinary Sodium Excretion ◽  
Systemic Blood Pressure ◽  
Synthesis Inhibitor ◽  
Renal Changes ◽  
Dose Dependent

The dose-dependent effects of intravenous infusions of nitric oxide (NO) synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 0.1, 1, 10, and 50 micrograms.kg-1.min-1), were studied in anesthetized rats to determine whether the inhibitory actions of L-NAME are manifested primarily in alterations of renal function or whether they are the consequences of the increase in systemic blood pressure. Mean arterial pressure (MAP) was not altered by the intravenous L-NAME infusions of 0.1 and 1.0 microgram.kg-1.min-1. However, 0.1 microgram.kg-1.min-1 L-NAME induced a 30% decrease in urine flow rate (UV). The administration of 1.0 microgram.kg-1.min-1 L-NAME, in addition to decreasing UV, also decreased urinary sodium excretion (UNaV) and renal plasma flow (RPF). The intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 intravenous L-NAME infusions of 10.0 and 50.0 microgram.kg-1.min-1 produced significant increases in MAP that reversed the initial fall in UV and UNaV, despite decreasing RPF and glomerular filtration rate (GFR). The administration of L-arginine alone (10 micrograms.kg-1.min-1) did not modify any of the parameters measured, but it effectively prevented all the hemodynamic and renal changes induced by the infusion of 50 micrograms.kg-1.min-1 L-NAME. These results suggest that the decrease in nitric oxide production induced by the intravenous infusion of L-NAME affects renal excretion of sodium and water in the absence of any significant change in blood pressure. At larger doses, L-NAME also produces hypertension that overrides the initial antinatriuretic effect.

scholarly journals Contribution of captopril thiol group to the prevention of spontaneous hypertension

2007 ◽  
pp. S41-S48
Author(s):  
O Pecháňová
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Ace Inhibitors ◽  
Thiol Group ◽  
No Synthase ◽  
Spontaneous Hypertension ◽  
Cgmp Level ◽  
Control Group ◽  
No Production ◽  
Enalapril Group

We aimed to compare the effect of angiotensin converting enzyme (ACE) inhibitors captopril (containing thiol group) and enalapril (without thiol group) on the development of spontaneous hypertension and to analyze mechanisms of their actions, particularly effects on oxidative stress and NO production. Six-week-old SHR were divided into three groups: control, group receiving captopril (50 mg/kg/day) or enalapril (50 mg/kg/day) for 6 weeks. At the end of experiment, systolic blood pressure (SBP) increased by 41 % in controls. Both captopril and enalapril prevented blood pressure increase, however, SBP in the captopril group (121+/-5 mmHg) was significantly lower than that in the enalapril group (140+/-5 mmHg). Concentration of conjugated dienes in the aorta was significantly lower in the captopril group compared to the enalapril group. Captopril and enalapril increased NO synthase activity in the heart and aorta to the similar level. Neither captopril nor enalapril was, however, able to increase the expression of eNOS. Both ACE inhibitors increased the level of cGMP. However, cGMP level was significantly higher in the aorta of captopril group. We conclude that captopril, beside inhibition of ACE, prevented hypertension by increasing NO synthase activity and by simultaneous decrease of oxidative stress which resulted in increase of cGMP concentration.

Abstract 111: Xanthine Oxidoreductase Plays a Key Role in Nitrate, Nitrite and Nitric Oxide Homeostasis When the Endothelial Nitric Oxide Synthase is Compromised

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Maria Peleli ◽  
Christa Zollbrecht ◽  
Marcelo Montenegro ◽  
Michael Hezel ◽  
Eddie Weitzberg ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Primary Source ◽  
No Production ◽  
Xanthine Oxidoreductase ◽  
Physiological Conditions ◽  
Inorganic Nitrate ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Xanthine oxidoreductase (XOR) is generally known as a source of superoxide production, but this enzyme has also been suggested to mediate NO production via reduction of inorganic nitrate (NO 3 - ) and nitrite(NO 2 - ). This pathway for NO generation is of particular importance during certain pathologies, whereas endothelial NO synthase (eNOS) is the primary source of vascular NO generation under normal physiological conditions. The exact interplay between the NOS and XOR-derived NO is not yet fully elucidated. The aim of the present study was to investigate if eNOS deficiency is partly compensated by XOR upregulation and sensitization of the NO 3 - - NO 2 - - NO pathway. NO 3 - and NO 2 - were similar between naïve eNOS KO and wildtype (wt) mice, but reduced upon chronic treatment with the non-selective NOS inhibitor L-NAME (wt: 25.0±5.2, eNOS KO: 39.2±6.4, L-NAME: 8.2±1.6 μ NO 3 - -, wt: 0.38±0.07, eNOS KO: 0.42±0.04, L-NAME: 0.12±0.02 μ NO 2 - ). XOR function was upregulated in eNOS KO compared with wt mice [(mRNA: wt 1±0.07, eNOS KO 1.38±0.17), (activity: wt 825±54, eNOS KO 1327±280 CLU/mg/min), (uric acid: wt 32.87±1.53, eNOS KO 43.23±3.54 μ)]. None of these markers of XOR activity was increased in nNOS KO and iNOS KO mice. Following acute dose of NO 3 - (10 mg/kg bw, i.p.), the increase of plasma NO 2 - was more pronounced in eNOS KO (+0.51±0.13 μ) compared with wt (+0.22±0.09 μ), and this augmented response in the eNOS KO was abolished by treatment with the highly selective XOR inhibitor febuxostat (FEB). Liver from eNOS KO had higher reducing capacity of NO 2 - to NO compared with wt, and this effect was attenuated by FEB (Δppb of NO: wt +8.7±4.2, eNOS KO +44.2±15.0, wt+FEB +22.2±9.6, eNOS KO+FEB +26.8±10.2). Treatment with FEB increased blood pressure in eNOS KO (ΔMAP:+10.2±5.6 mmHg), but had no effect in wt (ΔMAP:-0.6±3.3 mmHg). Supplementation with NO 3 - (10 mM, drinking water) reduced blood pressure in eNOS KO (ΔMAP: -6.3±2.2 mmHg), and this effect was abolished by FEB (ΔMAP: +1.1±1.9 mmHg). In conclusion, upregulated and altered XOR function in conditions with eNOS deficiency can facilitate the NO 3 - - NO 2 - - NO pathway and hence play a significant role in vascular NO homeostasis.

scholarly journals Methane-Rich Saline: A Potential Resuscitation Fluid for Hemorrhagic Shock

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Yingmu Tong ◽  
Yanyan Dong ◽  
Yang Feng ◽  
Zeyu Li ◽  
Yifan Jia ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Hemorrhagic Shock ◽  
Autologous Blood ◽  
Serum Levels ◽  
Systemic Blood Pressure ◽  
Multiple Organ ◽  
Shock Group ◽  
Control Group ◽  
Sham Control ◽  
Resuscitation Fluid

Hemorrhagic shock is caused by massive blood loss. If the patient is not fully resuscitated in time, this may eventually lead to multiple organ failure and even death. Previous studies on methane-rich saline in animal models showed that it confers resistance against many diseases. In this study, we explored the protective effect of methane-rich saline, used as a resuscitation fluid, in hemorrhagic shock. Hemorrhagic shock was induced in SD rats by bloodletting via intubation of the right femoral artery. The rats were divided into three groups: a sham control group (sham control), a shock group resuscitated by an infusion of autologous blood and an equivalent volume of normal saline (Shock+NS), and a shock group resuscitated by an infusion of autologous blood and an equivalent volume of methane-rich saline (Shock+MRS). Assessment of blood pressure and levels of plasma lactate showed that resuscitation using methane-rich saline (MRS) restored systemic blood pressure and reduced the levels of lactate in the plasma. Meanwhile, lower levels of serum IL-6 and TNF-α were also observed in the group resuscitated with MRS. In the heart, liver, and kidney, MRS reduced inflammation and oxidative stress levels. Analysis of organ function via levels of biochemical indicators revealed that the group resuscitated with MRS had reduced serum levels of AST and CK, indicating a potential cardioprotective effect. The expression levels of apoptosis-related proteins, including those of Bcl-2/Bax, and the results of TUNEL-labeling assay indicated that MRS significantly reduced apoptosis in the heart. Methane also had a positive effect on the expression of the PGC-1α/SIRT3/SOD2 signaling pathway. Our results showed that MRS can potentially serve as a novel resuscitation fluid because of its anti-inflammatory, antioxidative, and antiapoptotic properties.

scholarly journals The effect of chronic nitric oxide inhibition on vascular reactivity and blood pressure in pregnant rats

1999 ◽  
Vol 117 (5) ◽  
pp. 197-204 ◽  
Author(s):  
Nilton Hideto Takiuti ◽  
Maria Helena Cetelli Carvalho ◽  
Soubhi Kahhale ◽  
Dorothy Nigro ◽  
Hermes Vieira Barbeiro ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Vascular Reactivity ◽  
Unit Weight ◽  
Control Group ◽  
Pregnant Rats ◽  
Nitric Oxide Inhibition ◽  
Female Wistar Rats ◽  
Main Component ◽  
Oxide Inhibition

CONTEXT: The exact mechanism involved in changes in blood pressure and peripheral vascular resistance during pregnancy is unknown. OBJECTIVE:To evaluate the importance of endothelium-derivated relaxing factor (EDRF) and its main component, nitric oxide, in blood pressure and vascular reactivity in pregnant rats. DESIGN: Clinical trial in experimentation animals. SETTING: University laboratory of Pharmacology. SAMPLE: Female Wistar rats with normal blood pressure, weight (152 to 227 grams) and age (90 to 116 days). INTERVENTION: The rats were divided in to four groups: pregnant rats treated with L-NAME (13 rats); pregnant control rats (8 rats); virgin rats treated with L-NAME (10 rats); virgin control rats (12 rats). The vascular preparations and caudal blood pressure were obtained at the end of pregnancy, or after the administration of L-NAME in virgin rats. MAIN MEASUREMENTS: The caudal blood pressure and the vascular response to acetylcholine in pre-contracted aortic rings, both with and without endothelium, and the effect of nitric oxide inhibition, Nw-L-nitro-arginine methyl-ester (L-NAME), in pregnant and virgin rats. The L-NAME was administered in the drinking water over a 10-day period. RESULTS: The blood pressure decreased in pregnancy. Aortic rings of pregnant rats were more sensitive to acetylcholine than those of virgin rats. After L-NAME treatment, the blood pressure increased and relaxation was blocked in both groups. The fetal-placental unit weight of the L-NAME group was lower than that of the control group. CONCLUSION: Acetylcholine-induced vasorelaxation sensitivity was greater in pregnant rats and that blood pressure increased after L-NAME administration while the acetylcholine-induced vasorelaxation response was blocked.

scholarly journals The Effects of Oral l-Arginine and l-Citrulline Supplementation on Blood Pressure

Nutrients ◽  
2019 ◽  
Vol 11 (7) ◽  
pp. 1679 ◽  
Author(s):  
David Khalaf ◽  
Marcus Krüger ◽  
Markus Wehland ◽  
Manfred Infanger ◽  
Daniela Grimm
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Animal Studies ◽  
Current Data ◽  
No Production ◽  
First Pass Metabolism ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide ◽  
Antihypertensive Properties ◽  
Pass Metabolism

Nitric oxide (NO) is a well-known vasodilator produced by the vascular endothelium via the enzyme endothelial nitric oxide synthase (eNOS). The inadequate production of NO has been linked to elevated blood pressure (BP) in both human and animal studies, and might be due to substrate inaccessibility. This review aimed to investigate whether oral administration of the amino acids l-arginine (Arg) and l-citrulline (Cit), which are potential substrates for eNOS, could effectively reduce BP by increasing NO production. Both Arg and Cit are effective at increasing plasma Arg. Cit is approximately twice as potent, which is most likely due to a lower first-pass metabolism. The current data suggest that oral Arg supplementation can lower BP by 5.39/2.66 mmHg, which is an effect that is comparable with diet changes and exercise implementation. The antihypertensive properties of Cit are more questionable, but are likely in the range of 4.1/2.08 to 7.54/3.77 mmHg. The exact mechanism by which Cit and Arg exert their effect is not fully understood, as normal plasma Arg concentration greatly exceeds the Michaelis constant (Km) of eNOS. Thus, elevated plasma Arg concentrations would not be expected to increase endogenous NO production significantly, but have nonetheless been observed in other studies. This phenomenon is known as the “l-arginine paradox”.

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