scholarly journals Mitochondrial function and nitric oxide metabolism are modified by enalapril treatment in rat kidney

2007 ◽  
Vol 292 (4) ◽  
pp. R1494-R1501 ◽  
Author(s):  
Barbara Piotrkowski ◽  
Cesar G. Fraga ◽  
Elena M. V. de Cavanagh
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Mitochondrial Function ◽  
Uncoupling Protein ◽  
Rat Kidney ◽  
Blood Pressure Reduction ◽  
Renin Angiotensin System ◽  
Renal Protection ◽  
Kidney Mitochondria ◽  
Ras Inhibition

The renal and cardiac benefits of renin-angiotensin system (RAS) inhibition in hypertension exceed those attributable to blood pressure reduction, and seem to involve mitochondrial function changes. To investigate whether mitochondrial changes associated with RAS inhibition are related to changes in nitric oxide (NO) metabolism, four groups of male Wistar rats were treated during 2 wk with a RAS inhibitor, enalapril (10 mg·kg−1·day−1; Enal), or a NO synthase (NOS) inhibitor, Nω-nitro-l-arginine methyl ester (l-NAME) (1 mg·kg−1·day−1), or both (Enal+l-NAME), or were untreated (control). Blood pressure and body weight were lower in Enal than in control. Electron transfer through complexes I to III and cytochrome oxidase activity were significantly lower, and uncoupling protein-2 content was significantly higher in kidney mitochondria isolated from Enal than in those from control. All of these changes were prevented by l-NAME cotreatment and were accompanied by a higher production/bioavailability of kidney NO. l-NAME abolished mitochondrial NOS activity but failed to inhibit extra-mitochondrial kidney NOS, underscoring the relevance of mitochondrial NO in those effects of enalapril that were suppressed by l-NAME cotreatment. In Enal, kidney mitochondria H2O2 production rate and MnSOD activity were significantly lower than in control, and these effects were not prevented by l-NAME cotreatment. These findings may clarify the role of NO in the interactions between RAS and mitochondrial metabolism and can help to unravel the mechanisms involved in renal protection by RAS inhibitors.

Antihypertensive Property and Renal Protection by Shichimotsu-koka-to Extract in Salt-induced Hypertension in Dahl Strain Rats

1994 ◽  
Vol 22 (01) ◽  
pp. 51-62 ◽  
Author(s):  
Nobuhito Hiwara ◽  
Yoshio Uehara ◽  
Satoru Takada ◽  
Yukari Kawabata ◽  
Nobuko Ohshima ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Renal Function ◽  
Aortic Wall ◽  
Antihypertensive Effect ◽  
Blood Pressure Reduction ◽  
Glomerular Sclerosis ◽  
Pressure Reduction ◽  
Renal Protection ◽  
Induced Hypertension ◽  
Sclerotic Lesions

We determined whether or not the kampo formula, Shichimotsu-koka-to extract, attenuates the development of salt-induced hypertension and provides renal protection against hypertensive injury in Dahl salt-sensitive (Dahl S) rats. A six-week treatment using this formula dose-dependently decreased the systolic blood pressure in Dahl S rats fed a high-salt (2% NaCl) diet. This blood pressure reduction was associated with a decrease in the thickness of the aortic wall. Renal function was not altered with this treatment; however, glomerular sclerotic lesions in the kidney were significantly attenuated. Neither arterial nor tubular lesions were affected. These data suggest that Shichimotsu-koka-to extract exhibits an antihypertensive effect which is associated with partial resolution of glomerular sclerosis in the kidney.

Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats

2003 ◽  
Vol 285 (2) ◽  
pp. F295-F302 ◽  
Author(s):  
Mong-Heng Wang ◽  
Jishi Wang ◽  
Hsin-Hsin Chang ◽  
Barbara A. Zand ◽  
Miao Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Rat Kidney ◽  
Late Pregnancy ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Male Rats ◽  
Pregnant Rats ◽  
Renal Vasoconstriction ◽  
Dependent Inhibition

20-Hydroxyeicosatetraenoic acid (20-HETE), which promotes renal vasoconstriction, is formed in the rat kidney primarily by cytochrome P-450 (CYP) 4A isoforms (4A1, 4A2, 4A3, 4A8). Nitric oxide (NO) has been shown to bind to the heme moiety of the CYP4A2 protein and to inhibit 20-HETE synthesis in renal arterioles of male rats. However, it is not known whether NO interacts with and affects the activity of CYP4A1 and CYP4A3, the major renal CYP4A isoforms in female rats. Incubation of recombinant CYP4A1 and 4A3 proteins with sodium nitroprusside (SNP) shifted the absorbance at 440 nm, indicating the formation of a ferric-nitrosyl-CYP4A complex. The absorbance for CYP4A3 was about twofold higher than that of CYP4A1. Incubation of SNP or peroxynitrite (PN; 0.01–1 mM) with CYP4A recombinant membranes caused a concentration-dependent inhibition of 20-HETE synthesis, with both chemicals having a greater inhibitory effect on CYP4A3-catalyzed activity. Moreover, incubation of CYP4A1 and 4A3 proteins with PN (1 mM) resulted in nitration of tyrosine residues in both proteins. In addition, PN and SNP inhibited 20-HETE synthesis in renal microvessels from female rats by 65 and 59%, respectively. We previously showed that microvessel CYP4A1/CYP4A3 expression and 20-HETE synthesis are decreased in late pregnancy. Therefore, we investigated whether such a decrease is dependent on NO, the synthesis of which has been shown to increase in late pregnancy. Administration of NG-nitro-l-arginine methyl ester (l-NAME) to pregnant rats for 6 days ( days 15- 20 of pregnancy) caused a significant increase in systolic blood pressure, which was prevented by concurrent treatment with the CYP4A inhibitor 1-aminobenzotriazole (ABT). Urinary NO2/NO3 excretion decreased by 40 and 52% in l-NAME- and l-NAME + ABT-treated groups, respectively. Interestingly, renal microvessel 20-HETE synthesis showed a marked increase following l-NAME treatment, and this increase was diminished with coadministration of ABT. These results demonstrate that NO interacts with CYP4A proteins in a distinct manner and it interferes with renal microvessel 20-HETE synthesis, which may play an important role in the regulation of blood pressure and renal function during pregnancy.

scholarly journals Blood pressure reduction and RAAS inhibition in diabetic kidney disease: therapeutic potentials and limitations

2020 ◽  
Vol 33 (5) ◽  
pp. 949-963
Author(s):  
Giovanna Leoncini ◽  
Francesca Viazzi ◽  
Salvatore De Cosmo ◽  
Giuseppina Russo ◽  
Paola Fioretto ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Kidney Disease ◽  
Blood Pressure Control ◽  
Therapeutic Approach ◽  
Diabetic Kidney Disease ◽  
Blood Pressure Reduction ◽  
Pressure Control ◽  
Renal Outcome ◽  
Renal Protection ◽  
Diabetic Kidney

Abstract Diabetic kidney disease (DKD) affects approximately one-third of patients with diabetes and taking into consideration the high cardiovascular risk burden associated to this condition a multifactorial therapeutic approach is traditionally recommended, in which glucose and blood pressure control play a central role. The inhibition of renin–angiotensin–aldosterone RAAS system represent traditionally the cornerstone of DKD. Clinical outcome trials have demonstrated clinical significant benefit in slowing nephropathy progression mainly in the presence of albuminuria. Thus, international guidelines mandate their use in such patients. Given the central role of RAAS activity in the pathogenesis and progression of renal and cardiovascular damage, a more profound inhibition of the system by the use of multiple agents has been proposed in the past, especially in the presence of proteinuria, however clinical trials have failed to confirm the usefulness of this therapeutic approach. Furthermore, whether strict blood pressure control and pharmacologic RAAS inhibition entails a favorable renal outcome in non-albuminuric patients is at present unclear. This aspect is becoming an important issue in the management of DKD since nonalbuminuric DKD is currently the prevailing presenting phenotype. For these reasons it would be advisable that blood pressure management should be tailored in each subject on the basis of the renal phenotype as well as related comorbidities. This article reviews the current literature and discusses potentials and limitation of targeting the RAAS in order to provide the greatest renal protection in DKD.

scholarly journals Intermedin ameliorates vascular and renal injury by inhibition of oxidative stress

2008 ◽  
Vol 295 (6) ◽  
pp. F1735-F1743 ◽  
Author(s):  
Makoto Hagiwara ◽  
Grant Bledsoe ◽  
Zhi-Rong Yang ◽  
Robert S. Smith ◽  
Lee Chao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Transforming Growth Factor ◽  
Rat Kidney ◽  
Urine Volume ◽  
Intercellular Adhesion Molecule ◽  
Protective Agent ◽  
Glomerular Injury ◽  
Intercellular Adhesion Molecule 1 ◽  
Renal Protection

Intermedin (IMD) is a newly discovered peptide related to calcitonin gene-related peptide and adrenomedullin, and has been shown to reduce blood pressure and reactive oxygen species formation in vivo. In this study, we determined whether IMD exerts vascular and renal protection in DOCA-salt hypertensive rats by intravenous injection of adenovirus harboring the human IMD gene. Expression of human IMD was detected in the rat kidney via immunohistochemistry. IMD administration significantly lowered blood pressure, increased urine volume, and restored creatinine clearance. IMD also dramatically decreased superoxide formation and media thickness in the aorta. Vascular injury in the kidney was reduced by IMD gene delivery as evidenced by the prevention of glomerular and peritubular capillary loss. Moreover, IMD lessened morphological damage of the renal tubulointerstitium and reduced glomerular injury and hypertrophy. Attenuation of inflammatory cell accumulation in the kidney by IMD was accompanied by inhibition of p38MAPK activation and intercellular adhesion molecule 1 expression. In addition, IMD gene transfer resulted in a marked decline in myofibroblast and collagen accumulation in association with decreased transforming growth factor-β1 levels. Furthermore, IMD increased nitric oxide excretion in the urine and lowered the amount of lipid peroxidation. These results demonstrate that IMD is a powerful renal protective agent with pleiotropic effects by preventing endothelial cell loss, kidney damage, inflammation, and fibrosis in hypertensive DOCA-salt rats via inhibition of oxidative stress and proinflammatory mediator pathways.

Differential effect of tetradecythioacetic acid on the renin-angiotensin system and blood pressure in SHR and 2-kidney, 1-clip hypertension

2007 ◽  
Vol 293 (3) ◽  
pp. F839-F845 ◽  
Author(s):  
Liliana Monica Bivol ◽  
Rolf Kristian Berge ◽  
Bjarne Magnus Iversen
Keyword(s):  
Blood Pressure ◽  
Blood Pressure Reduction ◽  
Kidney Tissue ◽  
Renin Angiotensin System ◽  
Minor Effect ◽  
Ang Ii ◽  
Hypertensive Rats ◽  
Blood Pressure Lowering Effect ◽  
Angiotensin System ◽  
Renin Angiotensin

The tetradecythioacetic acid (TTA) is a modified fatty acid known to exhibit pleiotropic effects. First, we compared the effect of TTA on the blood pressure in spontaneously hypertensive rats (SHR) with two-kidney, one-clip (2K1C)-hypertensive rats. Second, we examined mechanisms involved in the blood pressure reduction. TTA had minor effect on systolic blood pressure (SBP) in young SHR up to 8 wk of age. In 2K1C we confirmed the blood pressure-lowering effect of TTA (SBP: 173 ± 4 before vs. 138 ± 3 mmHg after TTA, P < 0.001). No effect on SBP was seen in Wistar-Kyoto rat (WKY) controls. Plasma renin activity (PRA) was low in SHR and WKY controls and TTA did not change it. PRA decreased from 22.9 ± 1.3 to 16.2 ± 2.2 ng·ml−1·h−1 ( P = 0.02) in 2K1C. Plasma ANG II concentration declined from 101 ± 3 to 81 ± 5 fmol/l after TTA treatment ( P = 0.005). In the clipped kidney, tissue ANG I concentration decreased from 933 ± 68 to 518 ± 60 fmol/g tissue ( P = 0.001), and ANG II decreased from 527 ± 38 to 149 ± 21 fmol/g tissue ( P < 0.001) after TTA treatment. In the nonclipped kidney, TTA did not change ANG I and moderately reduced ANG II levels. The renal blood flow response to injection of ANG II into the nonclipped kidney was blunted compared with controls and normalized with TTA treatment (10 ± 2 before vs. 20 ± 2%, P < 0.001). The results indicate that TTA downregulates the renin-angiotensin system in high renin animals but has no effect in low renin models.

scholarly journals Cycling above rather than below lactate threshold is more effective for nitric oxide release and post-exercise blood pressure reduction in individuals with type-2 diabetes

2013 ◽  
Vol 19 (3) ◽  
pp. 633-640 ◽  
Author(s):  
Ricardo Yukio Asano ◽  
Rodrigo Alberto Vieira Browne ◽  
Rafael da Costa Sotero ◽  
Marcelo Magalhães Sales ◽  
José Fernando Vila Nova de Moraes ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Type 2 Diabetes ◽  
Lactate Threshold ◽  
Blood Pressure Reduction ◽  
Cycle Ergometer ◽  
Exercise Session ◽  
Post Exercise ◽  
Exercise Blood Pressure

The purposes of this study were to analyze and compare the effects of exercise performed in different intensities, above and below lactate threshold (LT) on post-exercise blood pressure (BP) and nitric oxide (NO) responses in individuals with type 2 diabetes (T2D). For this, 11 T2D underwent the following sessions: 1) control session; 2) 20-min of moderate cycling (80% LT); and 3) 20-min of high intensity cycling (120%LT) on a cycle ergometer. Plasma NO and BP measurements were carried out at rest and at 15 and 45 min of post-sessions. When compared to rest, only the exercise session performed at 120%LT elicited an increase of NO (from 7.2 to 9.5 µM, p<0.05), as well as a decrease in systolic BP (from 126.6±7.9 to 118.7±3.9 mmHg, p<0.05) during the post-exercise period. In conclusion, the results suggest that NO release and post-exercise BP decrease are intensity-dependent for individuals with T2D.

scholarly journals Nitric oxide enhancement and blood pressure decrease in patients with metabolic syndrome using soy protein or fish oil

2010 ◽  
Vol 54 (6) ◽  
pp. 540-545 ◽  
Author(s):  
Andréa Name Colado Simão ◽  
Marcell Alysson Batisti Lozovoy ◽  
Tathiana Name Colado Simão ◽  
Jane Bandeira Dichi ◽  
Tiemi Matsuo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Fatty Acids ◽  
Fish Oil ◽  
Soy Protein ◽  
Diastolic Pressure ◽  
Blood Pressure Reduction ◽  
Systolic Pressure ◽  
Randomized Design

OBJECTIVE: To verify the effects of fish oil and soy on nitric oxide (NO) and blood pressure in patients with metabolic syndrome (MS). SUBJECTS AND METHODS: Sixty women with MS were investigated in a parallel randomized design study. The first group maintained their usual diet; the second group received 25 g/day of soy; the third group received 3 g/day of n-3 fatty acids, and the fourth group the same amount previously cited of n-3 fatty acids and soy. RESULTS: Serum nitric oxide metabolites showed significant increase after 90 days in the fish oil and soy groups. Systolic pressure reduced after 45 days of treatment with fish oil, whereas diastolic pressure decreased significantly throughout the study in the soy group. CONCLUSIONS: NO increase and blood pressure reduction with fish oil or soy protein reinforce the importance of the influence of NO on blood pressure in patients with MS.

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