scholarly journals Participation of nitric oxide in different models of experimental hypertension

2008 ◽  
pp. 813-825
Author(s):  
J Török
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nervous Activity ◽  
Sympathetic Nervous Activity ◽  
Experimental Hypertension ◽  
No Production ◽  
Common Denominator ◽  
Blood Pressure Elevation ◽  
Functional Changes ◽  
Wide Range

This review concerns the role of nitric oxide (NO) in the pathogenesis of different models of experimental hypertension (NO-deficient, genetic, salt-dependent), which are characterized by a wide range of etiology. Although the contribution of NO may vary between different models of hypertension, a unifying characteristic of these models is the presence of oxidative stress that participates in the maintenance of elevated arterial pressure and seems to be a common denominator underlying endothelial dysfunction in various forms of experimental hypertension. Besides the imbalance between the endothelial production of vasorelaxing and vasoconstricting compounds as well as the relative insufficiency of vasodilator systems to compensate augmented vasoconstrictor systems, there were found numerous structural and functional abnormalities in blood vessels and heart of hypertensive animals. The administration of antihypertensive drugs, antioxidants and NO donors is capable to attenuate blood pressure elevation and to improve morphological and functional changes of cardiovascular system in some but not all hypertensive models. The failure to correct spontaneous hypertension by NO donor administration reflects the fact that sympathetic overactivity plays a key role in this form of hypertension, while NO production in spontaneously hypertensive rats might be enhanced to compensate increased blood pressure. A special attention should be paid to the modulation of sympathetic nervous activity in central and peripheral nervous system. These results extend our knowledge on the control of the balance between NO and reactive oxygen species production and are likely to be a basis for the development of new approaches to the therapy of diseases associated with NO deficiency.

The Hypothalamus and Hypertension

2001 ◽  
Vol 81 (4) ◽  
pp. 1599-1658 ◽  
Author(s):  
H. E. De Wardener
Keyword(s):  
Nitric Oxide ◽  
Renal Mass ◽  
Nervous Activity ◽  
Corticotropin Releasing Factor ◽  
Sympathetic Nervous Activity ◽  
Afferent Stimulation ◽  
Functional Changes ◽  
Impaired Ability ◽  
Sympathetic Nervous ◽  
Young Rat

Most forms of hypertension are associated with a wide variety of functional changes in the hypothalamus. Alterations in the following substances are discussed: catecholamines, acetylcholine, angiotensin II, natriuretic peptides, vasopressin, nitric oxide, serotonin, GABA, ouabain, neuropeptide Y, opioids, bradykinin, thyrotropin-releasing factor, vasoactive intestinal polypeptide, tachykinins, histamine, and corticotropin-releasing factor. Functional changes in these substances occur throughout the hypothalamus but are particularly prominent rostrally; most lead to an increase in sympathetic nervous activity which is responsible for the rise in arterial pressure. A few appear to be depressor compensatory changes. The majority of the hypothalamic changes begin as the pressure rises and are particularly prominent in the young rat; subsequently they tend to fluctuate and overall to diminish with age. It is proposed that, with the possible exception of the Dahl salt-sensitive rat, the hypothalamic changes associated with hypertension are caused by renal and intrathoracic cardiopulmonary afferent stimulation. Renal afferent stimulation occurs as a result of renal ischemia and trauma as in the reduced renal mass rat. It is suggested that afferents from the chest arise, at least in part, from the observed increase in left auricular pressure which, it is submitted, is due to the associated documented impaired ability to excrete sodium. It is proposed, therefore, that the hypothalamic changes in hypertension are a link in an integrated compensatory natriuretic response to the kidney's impaired ability to excrete sodium.

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.

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.

Evidence That Reduced Renal Medullary NOS Activity of Dahl S Rats Enables Small Elevations of Avp to Produce Sustained Hypertension

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 682-682
Author(s):  
Baozhi Yuan ◽  
Allen W Cowley
Keyword(s):  
Nitric Oxide ◽  
Control Level ◽  
Renal Medulla ◽  
Renal Tissue ◽  
Brown Norway ◽  
Experimental Hypertension ◽  
Chronic Hypertension ◽  
No Production ◽  
Potent Vasoconstrictor ◽  
Plasma Arginine

27 It remains unclear why sustained elevations of plasma arginine vasopressin (AVP), a potent vasoconstrictor and fluid retaining hormone, do not generally result in hypertension. Related to this, there have been 4 general observations: 1) AVP is elevated in many forms of human and experimental hypertension, including Dahl S rats; 2) AVP can stimulate nitric oxide synthases (NOS) and nitric oxide (NO) production in the renal medulla of normal rats; 3) AVP stimulated NO production can buffer AVP induced reductions of medullary blood flow; 4) partial reduction of medullary NOS activity (via medullary L-NAME infusion) unmasks chronic hypertensive effects of small elevations of plasma AVP (Hypertension. 2000; 35:740-745). In the present study, we hypothesize that Dahl salt-sensitive rats (DS) have reduced capacity to synthesize medullary NO which sensitizes them to the hypertensive effects of small elevations of circulating AVP. DS and Brown Norway (BN) rats with implanted arterial and venous catheters were fed a 0.4% salt diet and infused continuously for 14 days with a chronic “subpressor” dose of AVP (2 ng/kg/min). Conscious mean arterial pressure (MAP) was measured 2 hours daily with rats maintained in their home cages. MAP in DS rats increased during day1 of AVP infusion from a control level of 127 ± 0.9 mmHg to an average of 147 ± 1.6 mmHg after 14 days. MAP did not return to control values even within three days following the end of AVP infusion. BN rats showed no changes of MAP during 14 days of AVP infusion (90.4 ± 0.6 mmHg and 92.3 ± 0.4 mmHg). Northern blot analysis of renal tissue from vehicle (saline) infused rats demonstrated that NOS I and NOS III mRNA expression was significantly less in DS rats in the renal outer medulla compared to BN rats. We conclude that small, normally subpressor elevations of plasma AVP can produce chronic hypertension in DS rats, a phenomenon probably related to reduced renal medullary NO synthesis.

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”.

scholarly journals Effect of Cadmium Exposure in Polymorphisms Gene NOS3, Blood Cadmium Level, Nitric Oxide Level, Blood Pressure and Antioxidant Enzymes

2018 ◽  
Vol 73 ◽  
pp. 06006
Author(s):  
Hernayanti ◽  
Santoso Slamet ◽  
Lestari Sri
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Antioxidant Enzyme ◽  
Human Life ◽  
The Body ◽  
No Production ◽  
Textile Materials ◽  
Length Polymorphisms ◽  
Exposed Individual ◽  
Result Show

Cadmium is one of a heavy metal which widely used in human life, especially in the electroplating industry and a mixture of textile materials. Cadmium that enters the body binds to the metallothioneins protein. It can increase the formation of free radical compounds, there by inhibiting enzyme activity such as nitric oxide synthase3. This gene regulates the expression of endothelial nitric oxide synthase which produce a nitric oxide. Nitric oxide role in regulated blood pressure as vasodilator with Angiotensin II as vasoconstriction. The susceptibility to Cd exposure will elevate if the polymorphisms of gene is found in population. The aim of this research was to know effect of cadmium to gene NOS3 polymorphisms on NO, systolic and diastolic blood pressure and antioxidant enzyme in Cd-exposed individual. The genotype individual were detected by Polymerase Chain Reaction-Restriction Fragment Length Polymorphisms (PCR-RLFP) with MBo1 restriction enzyme. Parameter recorded were blood Cd , NO level, SOD, systolic and diastolic. Data were analyzed by independent t-test. These result showed that 20% of 40 individual of cases subject were detected as polymorphisms individual of NOS3gene, with GA genotype. Their fragment DNA located on 206 bp, 119 bp and 87 bp, but non polymorphisms of NO gene is only located on 206 bp. The result show cadmium could influence polymorphisms NOS3gene and decrease NO production followed by increasing of blood pressure both systolic and diastolic. Cadmium also decrease antioxidant enzyme SOD and GPx level.

Hypoxemia raises muscle sympathetic activity but not norepinephrine in resting humans

1989 ◽  
Vol 66 (4) ◽  
pp. 1736-1743 ◽  
Author(s):  
L. B. Rowell ◽  
D. G. Johnson ◽  
P. B. Chase ◽  
K. A. Comess ◽  
D. R. Seals
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Nervous Activity ◽  
Plasma Concentrations ◽  
Random Order ◽  
Sympathetic Nervous Activity ◽  
Severe Hypoxemia ◽  
Arterial Blood ◽  
End Tidal ◽  
Venous Plasma

The experimental objective was to determine whether moderate to severe hypoxemia increases skeletal muscle sympathetic nervous activity (MSNA) in resting humans without increasing venous plasma concentrations of norepinephrine (NE) and epinephrine (E). In nine healthy subjects (20–34 yr), we measured MSNA (peroneal nerve), venous plasma levels of NE and E, arterial blood pressure, heart rate, and end-tidal O2 and CO2 before (control) and during breathing of 1) 12% O2 for 20 min, 2) 10% O2 for 20 min, and 3) 8% O2 for 10 min--in random order. MSNA increased above control in five, six, and all nine subjects during 12, 10, and 8% O2, respectively (P less than 0.01), but only after delays of 12 (12% O2) and 4 min (8 and 10% O2). MSNA (total activity) rose 83 +/- 20, 260 +/- 146, and 298 +/- 109% (SE) above control by the final minute of breathing 12, 10, and 8% O2, respectively. NE did not rise above control at any level of hypoxemia; E rose slightly (P less than 0.05) at one time only with both 10 and 8% O2. Individual changes in MSNA during hypoxemia were unrelated to elevations in heart rate or decrements in blood pressure and end-tidal CO2--neither of which always fell. We conclude that in contrast to some other sympathoexcitatory stimuli such as exercise or cold stress, moderate to severe hypoxemia increases leg MSNA without raising plasma NE in resting humans.

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