Comparison of Combination Therapy of Olmesartan plus Azelnidipine or Hydrochlorothiazide on Renal and Vascular Damage in SHR/NDmcr-cp Rats

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Background: Although the recommended target blood pressure for patients with chronic kidney disease is <130/80 mm Hg, this is difficult to achieve by treatment with an angiotensin receptor blocker alone. Addition of either a calcium channel blocker or a diuretic is suggested as second-line medication; however, which combination is most beneficial for target-organ protection remains unknown. Methods: SHR/NDmcr-cp rats were administered no medications (control) or low-dose olmesartan for 2 weeks and then either olmesartan at an increased dose, azelnidipine, or the hydrochlorothiazide for 3 weeks. We assessed oxidative stress in the kidney and aorta, and endothelial function. Results: Urinary protein excretion was lower in all treated rats than in control rats. Oxidative stress caused by activation of NAD(P)H oxidase was observed in the glomeruli and aorta of control rats and was significantly suppressed in the olmesartan/azelnidipine (Olm/Azl) groups. Combination therapy with olmesartan and hydrochlorothiazide (Olm/HCTZ) however failed to suppress oxidative stress. The Olm/Azl groups maintained the endothelial surface layer in the glomeruli and protected endothelial function in the aorta. Conclusion: In an animal model of metabolic syndrome, a combination of Olm/Azl is superior to a combination of Olm/HCTZ in terms of prevention of glomerular and vascular injuries.

Related collections

Most cited references 33

Record: found
Abstract: found
Article: not found

Influence of heart rate on mortality among persons with hypertension: the Framingham Study.

W Kannel, R D'Agostino, Stacey A Bélanger … (1993)

Previous studies have shown positive associations between heart rate and both all-cause and cardiovascular mortality. These relationships, however, have not been investigated in persons with hypertension. Using 36-year follow-up data from the Framingham Study, we evaluated from 4530 subjects, aged 35 to 74, whose blood pressures were > or = 140 mm Hg systolic or > or = 90 mm Hg diastolic and who were not treated with antihypertensive medication. We used pooled logistic regression to calculate biennial mortality rates. Odds ratios and 95% confidence intervals for each increment in heart rate of 40 beats/min, adjusted for age and systolic blood pressure level, were: for all-cause mortality, 2.18 (1.68, 2.83) for men and 2.14 (1.59, 2.88) for women; and for cardiovascular mortality, 1.68 (1.19, 2.37) for men and 1.70 (1.08, 2.67) for women. Exclusion of outcomes in the first 2 or 4 years after measurement of heart rate did not materially change the results, which suggests that rapid heart is not merely an indicator of preexisting illness. Therefore heart rate may be an independent risk factor for cardiovascular death in persons with hypertension.

0 comments Cited 84 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Sympathetic hyperactivity in chronic kidney disease: pathogenesis, clinical relevance, and treatment.

Gerry Ligtenberg, Marlise Klein, Peter J. Blankestijn … (2004)

Cardiovascular morbidity and mortality importantly influence live expectancy of patients with chronic renal disease (CKD). Traditional risk factors are usually present, but several other factors have recently been identified. There is now evidence that CKD is often characterized by an activated sympathetic nervous system. This may contribute to the pathogenesis of renal hypertension, but it may also adversely affect prognosis independently of its effect on blood pressure. The purpose of this review is to summarize available knowledge on the role of the sympathetic nervous system in the pathogenesis of renal hypertension, its clinical relevance, and the consequences of this knowledge for the choice of treatment.

0 comments Cited 69 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

NAD(P)H oxidase and uncoupled nitric oxide synthase are major sources of glomerular superoxide in rats with experimental diabetic nephropathy.

Naoki Kashihara, Katsuhiko Tsujioka, Norio Komai … (2005)

Increased production of reactive oxygen species (ROS) in diabetes may be a common pathway linking diverse pathogenic mechanisms of diabetic vascular complications, including nephropathy. Assessment of the oxidative stress production pathway is therefore important for the prediction and prevention of diabetic complications. However, ROS production mechanisms remain unclear in diabetic glomeruli. To identify the source and determine the mechanisms of ROS production in the diabetic kidney, diabetes was induced with streptozotocin in rats. After 6 wk, glomerular ROS production had increased in the streptozotocin rat kidney, as assessed by dihydroethidium-derived chemiluminescence. ROS production was increased by the addition of NADH or L-arginine and was partially reduced by the addition of diphenylene iodonium or N(G)-nitro-L-arginine methyl ester, identifying NAD(P)H oxidase and nitric oxide (NO) synthase (NOS) as ROS sources. The mRNA and protein expression of endothelial NOS (eNOS), as measured by real-time RT-PCR and Western blotting, increased significantly (mRNA level, 1.3-fold; protein level, 1.8-fold). However, the dimeric form of eNOS was decreased in diabetic glomeruli, as measured by low-temperature SDS-PAGE. Production of renal ROS and NO by uncoupled NOS was imaged by confocal laser microscopy after renal perfusion of 2',7'-dichlorofluorescein diacetate (a ROS marker) and diaminorhodamine-4M AM (a NO marker) with L-arginine. Accelerated ROS production and diminished bioavailable NO caused by NOS uncoupling were noted in the diabetic kidney. Administration of tetrahydrobiopterin (BH4), a cofactor for eNOS, reversed the decreased dimeric form of eNOS and glomerular NO production. Our results indicate that NAD(P)H oxidase and uncoupling of eNOS contribute to glomerular ROS production, mediated by the loss of BH4 availability. These mechanisms are potential key targets for therapeutic interventions.

0 comments Cited 67 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (publisher-id): KBR

Journal ID (nlm-ta): Kidney Blood Press Res

Journal ID (doi): 10.1159/issn.1420-4096

Title: Kidney and Blood Pressure Research

Publisher: S. Karger AG

ISSN (Print): 1420-4096

ISSN (Electronic): 1423-0143

Publication date Subscription-year: 2011

Publication date (Print): March 2011

Publication date (Electronic): 27 January 2011

Volume: 34

Issue: 2

Pages: 87-96

Affiliations

Department of Nephrology and Hypertension, Kawasaki Medical School, Kurashiki, Japan

Author notes

*Hajime Nagasu, MD, Department of Nephrology and Hypertension, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0192 (Japan), E-Mail zajiten1@gmail.com

Article

Publisher ID: 323535 Other ID: Kidney Blood Press Res 2011;34:87–96

DOI: 10.1159/000323535

PubMed ID: 21273789

SO-VID: e9eced78-a47d-426a-875f-e70d9055660e

License:

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

History

Date received : 24 August 2010

Date accepted : 08 December 2010

Page count

Figures: 8, Tables: 1, Pages: 10

Comments

Comment on this article

scite_

Cited by 4

See all cited by

Most referenced authors 858

See all reference authors

- Version 1

Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

Submit here before September 30, 2024

Comparison of Combination Therapy of Olmesartan plus Azelnidipine or Hydrochlorothiazide on Renal and Vascular Damage in SHR/NDmcr-cp Rats

Read this article at

Abstract

Related collections

Karger: Nephrology

Most cited references 33

Influence of heart rate on mortality among persons with hypertension: the Framingham Study.

Sympathetic hyperactivity in chronic kidney disease: pathogenesis, clinical relevance, and treatment.

NAD(P)H oxidase and uncoupled nitric oxide synthase are major sources of glomerular superoxide in rats with experimental diabetic nephropathy.

Author and article information

Journal

Affiliations

Author notes

Article

History

Page count

Categories

Comments

Comment on this article

Similar content 204

Cited by 4

Most referenced authors 858