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Vol. 38, No. 1, 2001
Issue release date: January–February 2001
Section title: Research Paper
J Vasc Res 2001;38:39–46
(DOI:10.1159/000051028)

Nitric Oxide, Peroxynitrite and cGMP in Atherosclerosis-Induced Hypertension in Rabbits: Beneficial Effects of Cicletanine

Szilvássy Z. · Csont T. · Páli T. · Droy-Lefaix M.-T. · Ferdinandy P.
aDepartment of Pharmacology, University of Debrecen, Debrecen, bCardiovascular Research Group, Department of Biochemistry, University of Szeged, cDepartment of Biophysics, Biological Research Center, Szeged, Hungary, and dIPSEN-Beaufour, Paris, France

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Article / Publication Details

First-Page Preview
Abstract of Research Paper

Published online: 2/8/2001

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 1

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: http://www.karger.com/JVR

Abstract

We studied the effect of the furopyridine derivative antihypertensive drug, cicletanine, on blood pressure, vascular nitric oxide (NO) and cyclic guanosine 3′:5′-monophosphate (cGMP) content in the aorta and the renal and carotid arteries, aortic superoxide production, and serum nitrotyrosine level in hypertensive/atherosclerotic rabbits. The effect of cicletanine was compared to that of furosemide. Rabbits were fed a normal or a cholesterol-enriched (1.5%) diet over 8 weeks. On the 8th week, the rabbits were treated per os with 2 × 50 mg/kg daily doses of cicletanine, furosemide, or vehicle for 5 days (n = 5–6 in each groups). The cholesterol diet increased mean arterial blood pressure (MABP) from 86 ± 1 to 94 ± 2 mm Hg (p < 0.05). Cicletanine decreased MABP in atherosclerotic rabbits to 85 ± 1 mm Hg (p < 0.05), but it did not affect MABP in normal animals. Furosemide was without effect in both groups. In normal animals, NO content (assessed by electron spin resonance after in vivo spin trapping) in the aorta and the renal and carotid arteries was increased by cicletanine, and the drug increased cGMP in the renal artery as measured by radioimmunoassay. The cholesterol-enriched diet decreased both vascular NO and cGMP and increased aortic superoxide production assessed by lucigenin-enhanced chemiluminescence and serum nitrotyrosine determined by ELISA. In atherosclerotic animals, cicletanine increased NO and cGMP content in the aorta and the renal and carotid arteries and decreased aortic superoxide production and serum nitrotyrosine. Furosemide did not influence these parameters. We conclude that cicletanine lowers blood pressure in hypertensive/atherosclerotic rabbits. The antihypertensive effect of the drug in atherosclerosis may be based on its beneficial effects on the vascular NO-cGMP system and on the formation of reactive oxygen species.


  

Author Contacts

Dr. Péter Ferdinandy, Associate Professor
Cardiovascular Research Group, Department of Biochemistry
University of Szeged, Dóm tér 9, H–6720 Szeged (Hungary)
Tel. +36 62 545096, Fax +36 62 455097
E-Mail peter@biochem.szote.u-szeged-hu, http://www.cardiovasc.com/

  

Article Information

Received: Received: April 14, 1999
Accepted after revision: August 15, 2000
Number of Print Pages : 8
Number of Figures : 4, Number of Tables : 1, Number of References : 51

  

Publication Details

Journal of Vascular Research
Founded 1964 as Angiologica by M. Comèl and L. Laszt (1964–1973) continued as Blood Vessels by J.A. Bevan (1974–1991)

Vol. 38, No. 1, Year 2001 (Cover Date: January-February 2001)

Journal Editor: M.J. Mulvany, Aarhus
ISSN: 1018–1172 (print), 1423–0135 (Online)

For additional information: http://www.karger.com/journals/jvr


Article / Publication Details

First-Page Preview
Abstract of Research Paper

Published online: 2/8/2001

Number of Print Pages: 8
Number of Figures: 4
Number of Tables: 1

ISSN: 1018-1172 (Print)
eISSN: 1423-0135 (Online)

For additional information: http://www.karger.com/JVR


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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 goverment 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.
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