scholarly journals Inhibition of natriuretic factors increases blood pressure in rats

2009 ◽  
Vol 297 (2) ◽  
pp. F397-F402 ◽  
Author(s):  
Anees Ahmad Banday ◽  
Mustafa F. Lokhandwala
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Atpase Activity ◽  
Sodium Intake ◽  
D1 Receptor ◽  
Dopamine Level ◽  
Receptor Signaling ◽  
Proximal Tubular ◽  
Urinary Dopamine ◽  
Natriuretic Factors

Renal dopamine and nitric oxide contribute to natriuresis during high-salt intake which maintains sodium and blood pressure homeostasis. We wanted to determine whether concurrent inhibition of these natriuretic factors increases blood pressure during high-sodium intake. Male Sprague-Dawley rats were divided into the following groups: 1) vehicle (V)-tap water, 2) NaCl-1% NaCl drinking water, 3) 30 mM l-buthionine sulfoximine (BSO), an oxidant, 4) BSO plus NaCl, and 5) BSO plus NaCl with 1 mM tempol (antioxidant). Compared with V, NaCl intake for 10 days doubled sodium intake and increased urinary dopamine level but reduced urinary nitric oxide content. NaCl intake also reduced basal renal proximal tubular Na-K-ATPase activity with no effect on blood pressure. However, NaCl intake in BSO-treated rats failed to reduce basal Na-K-ATPase activity despite higher urinary dopamine levels. Also, dopamine failed to inhibit proximal tubular Na-K-ATPase activity and these rats exhibited reduced urinary nitric oxide levels and high blood pressure. Tempol supplementation in NaCl plus BSO-treated rats reduced blood pressure. BSO treatment alone did not affect the urinary nitric oxide and dopamine levels or blood pressure. However, dopamine failed to inhibit proximal tubular Na-K-ATPase activity in BSO-treated rats. BSO treatment also increased basal protein kinase C activity, D1 receptor serine phosphorylation, and oxidative markers like malondialdehyde and 8-isoprostane. We suggest that NaCl-mediated reduction in nitric oxide does not increase blood pressure due to activation of D1 receptor signaling. Conversely, oxidative stress-provoked inhibition of D1 receptor signaling fails to elevate blood pressure due to presence of normal nitric oxide. However, simultaneously decreasing nitric oxide levels with NaCl and inhibiting D1 receptor signaling with BSO elevated blood pressure.

Renal and cardiac oxidative/nitrosative stress in salt-loaded pregnant rat

2007 ◽  
Vol 293 (4) ◽  
pp. R1657-R1665 ◽  
Author(s):  
Annie Beauséjour ◽  
Véronique Houde ◽  
Karine Bibeau ◽  
Rébecca Gaudet ◽  
Jean St-Louis ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitrosative Stress ◽  
Gestational Hypertension ◽  
Sodium Intake ◽  
Pregnant Rats ◽  
High Sodium ◽  
High Sodium Intake ◽  
Arterial Blood ◽  
Cardiac Ventricle

Sodium supplementation given for 1 wk to nonpregnant rats induces changes that are adequate to maintain renal and circulatory homeostasis as well as arterial blood pressure. However, in pregnant rats, proteinuria, fetal growth restriction, and placental oxidative stress are observed. Moreover, the decrease in blood pressure and expansion of circulatory volume, normally associated with pregnancy, are prevented by high-sodium intake. We hypothesized that, in these pregnant rats, a loss of the balance between prooxidation and antioxidation, particularly in kidneys and heart, disturbs the normal course of pregnancy and leads to manifestations such as gestational hypertension. We thus investigated the presence of oxidative/nitrosative stress in heart and kidneys following high-sodium intake in pregnant rats. Markers of this stress [8-isoprostaglandin F2α (8-iso-PGF2α) and nitrotyrosine], producer of nitric oxide [nitric oxide synthases (NOSs)], and antioxidants [superoxide dismutase (SOD) and catalase] were measured. Then, molecules (Na+-K+-ATPase and aconitase) or process [apoptosis (Bax and Bcl-2), inflammation (monocyte chemoattractant protein-1, connective tissue growth factor, and TNF-α)] susceptible to free radicals was determined. In kidneys from pregnant rats on 1.8% NaCl-water, NOSs, apoptotic index, and nitrotyrosine expression were increased, whereas Na+-K+-ATPase mRNA and activity were decreased. In the left cardiac ventricle of these rats, heightened nitrotyrosine, 8-iso-PGF2α, and catalase activity together with reduced endothelial NOS protein expression and SOD and aconitase activities were observed. These findings suggest that oxidative/nitrosative stress in kidney and left cardiac ventricle destabilizes the normal course of pregnancy and could lead to gestational hypertension.

scholarly journals Effect of dietary sodium on vasoconstriction and eNOS-mediated vascular relaxation in caveolin-1-deficient mice

2008 ◽  
Vol 294 (3) ◽  
pp. H1258-H1265 ◽  
Author(s):  
Luminita H. Pojoga ◽  
Tham M. Yao ◽  
Sumi Sinha ◽  
Reagan L. Ross ◽  
Jeffery C. Lin ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Vascular Function ◽  
Sodium Intake ◽  
Dietary Sodium ◽  
Vascular Relaxation ◽  
Enos Expression ◽  
Vascular Contraction ◽  
Caveolin 1 ◽  
Enos Activity

Changes in dietary sodium intake are associated with changes in vascular volume and reactivity that may be mediated, in part, by alterations in endothelial nitric oxide synthase (eNOS) activity. Caveolin-1 (Cav-1), a transmembrane anchoring protein in the plasma membrane caveolae, binds eNOS and limits its translocation and activation. To test the hypothesis that endothelial Cav-1 participates in the dietary sodium-mediated effects on vascular function, we assessed vascular responses and nitric oxide (NO)-mediated mechanisms of vascular relaxation in Cav-1 knockout mice (Cav-1−/−) and wild-type control mice (WT; Cav-1+/+) placed on a high-salt (HS; 4% NaCl) or low-salt (LS; 0.08% NaCl) diet for 16 days. After the systolic blood pressure was measured, the thoracic aorta was isolated for measurement of vascular reactivity and NO production, and the heart was used for measurement of eNOS expression and/or activity. The blood pressure was elevated in HS mice treated with NG-nitro-l-arginine methyl ester and more so in Cav-1−/− than WT mice and was significantly reduced during the LS diet. Phenylephrine caused vascular contraction that was significantly reduced in Cav-1−/− (maximum 0.25 ± 0.06 g/mg) compared with WT (0.75 ± 0.22 g/mg) on the HS diet, and the differences were eliminated with the LS diet. Also, vascular contraction in response to membrane depolarization by high KCl (96 mM) was reduced in Cav-1−/− (0.27 ± 0.05 g/mg) compared with WT mice (0.53 ± 0.12 g/mg) on the HS diet, suggesting that the reduced vascular contraction is not limited to a particular receptor. Acetylcholine (10−5 M) caused aortic relaxation in WT mice on HS (23.6 ± 3.5%) and LS (23.7 ± 5.5%) that was enhanced in Cav-1−/− HS (72.6 ± 6.1%) and more so in Cav-1−/− LS mice (93.6 ± 3.5%). RT-PCR analysis indicated increased eNOS mRNA expression in the aorta and heart, and Western blots indicated increased total eNOS and phosphorylated eNOS in the heart of Cav-1−/− compared with WT mice on the HS diet, and the genotypic differences were less apparent during the LS diet. Thus Cav-1 deficiency during the HS diet is associated with decreased vasoconstriction, increased vascular relaxation, and increased eNOS expression and activity, and these effects are altered during the LS diet. The data support the hypothesis that endothelial Cav-1, likely through an effect on eNOS activity, plays a prominent role in the regulation of vascular function during substantial changes in dietary sodium intake.

Interaction of nitric oxide and the cytochrome P-450 system on blood pressure and renal function in the rat: dependence on sodium intake

2010 ◽  
Vol 201 (4) ◽  
pp. 493-502 ◽  
Author(s):  
M. Kuczeriszka ◽  
K. H. Olszyński ◽  
A. Gąsiorowska ◽  
J. Sadowski ◽  
E. Kompanowska-Jezierska
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Renal Function ◽  
Sodium Intake ◽  
Cytochrome P 450

Effects of Neuroactive Amino Acids Derivatives on Cardiac and Cerebral Mitochondria and Endothelial functions in Animals Exposed to Stress

2017 ◽  
Vol 2 (2) ◽  
pp. 34
Author(s):  
TA Popova ◽  
II Prokofiev ◽  
IS Mokrousov ◽  
Valentina Perfilova ◽  
AV Borisov ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Platelet Aggregation ◽  
Atp Synthesis ◽  
Elevated Concentration ◽  
Blood Pressure Monitor ◽  
Pressure Monitor ◽  
Griess Reagent ◽  
Arterial Blood ◽  
Endothelial Functions

Introduction: To study the effects of glufimet, a new derivative of glutamic acid, and phenibut, a derivative of γ-aminobutyric acid (GABA), on cardiac and cerebral mitochondria and endothelial functions in animals following exposure to stress and inducible nitric oxide synthase (iNOS) inhibition. Methods: Rats suspended by their dorsal cervical skin fold for 24 hours served as the immobilization and pain stress model. Arterial blood pressure was determined using a non-invasive blood pressure monitor. Mitochondrial fraction of heart and brain homogenates were isolated by differential centrifugation and analysed for mitochondrial respiration intensity, lipid peroxidation (LPO) and antioxidant enzyme activity using polarographic method. The concentrations of nitric oxide (NO) terminal metabolites were measured using Griess reagent. Hemostasis indices were evaluated. Platelet aggregation was estimated using modified version of the Born method described by Gabbasov et al., 1989. Results: The present study demonstrated that stress leads to an elevated concentration of NO terminal metabolites and LPO products, decreased activity of antioxidant enzymes, reduced mitochondrial respiratory function, and endothelial dysfunction. Inhibition of iNOS by aminoguanidine had a protective effect. Phenibut and glufimet inhibited a rise in stress-induced nitric oxide production. This resulted in enhanced coupling of substrate peroxidation and ATP synthesis. The reduced LPO processes caused by glufimet and phenibut normalized the endothelial function which was proved by the absence of average daily blood pressure (BP) elevation episodes and a significant increase in platelet aggregation level. Conclusion: Glufimet and phenibut restrict the harmful effects of stress on the heart and brain possibly by modulating iNOS activity.

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