CoChat
Sign Up
Cited by 21Eicosanoids and Hypertension PharmacologyNitric Oxide and Endothelin EffectsInflammatory mediators and NSAID effects

Long-term fenofibrate treatment impairs endothelium-dependent dilation to acetylcholine by altering the cyclooxygenase pathway

BLANCORIVERO, J, MARQUEZRODAS, I, XAVIER, F, ARASLOPEZ, R, ARROYOVILLA, I, FERRER, M, BALFAGON, G·2007·Cardiovascular Research
DOI 10.1016/j.cardiores.2007.03.006
Open this paper in CoChat — free account

Abstract

OBJECTIVE: Experimental studies and opinion articles emphasize that cardiovascular alterations associated with ageing can be improved by the long-term use of fenofibrates. We analyzed the effect of fenofibrate treatment on the acetylcholine-induced relaxation in rat aorta and the participation of nitric oxide (NO) and cyclooxygenase (COX)-derived factors in this effect. METHODS: Acetylcholine relaxation in untreated and 6-week fenofibrate-treated Wistar rats was analyzed in the absence and presence of the NO synthase (NOS) inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME), the specific inducible NO (iNOS) synthase inhibitor 1400W, the nonspecific COX inhibitor indomethacin, the specific COX-2 inhibitor NS-398, the specific thromboxane receptor antagonist SQ-29548, the thromboxane synthesis inhibitor furegrelate, the prostacyclin synthesis inhibitor tranylcypromine, or the 20-HETES synthesis inhibitor formamidine. eNOS, iNOS, COX-1, and COX-2 expression was studied by Western blotting. In addition, production of prostaglandin F(2alpha) (PGF(2alpha)), thromboxane A(2) (TxA(2)), prostaglandin E(2) (PGE(2)), isoprostanes, and prostacyclin (PGI(2)) was also measured. RESULTS: Fenofibrate treatment reduced acetylcholine relaxation. Indomethacin, NS-398, and tranylcypromine decreased acetylcholine relaxation in untreated rats but enhanced relaxation in treated rats. SQ-29548 increased acetylcholine responses in segments from treated rats but not in segments from untreated rats. L-NAME decreased vasodilator response to acetylcholine in both groups while furegrelate, NS-398, 1400W, and formamidine did not affect acetylcholine responses in either group. eNOS and COX-2 expression was higher in aorta from treated rats while COX-1 and iNOS remained unmodified. Basal and acetylcholine-stimulated NO and PGE(2) release were increased, and that of PGI(2) decreased in treated rats. TxA(2) release was similar, but PGF(2alpha) release was undetectable in both groups. CONCLUSIONS: Although it increases NO production through increases in eNOS expression, fenofibrate treatment induces endothelial dysfunction. This effect seems to be mediated by decreased PGI(2) and increased PGE(2) release, and it may help to explain the rise in thromboembolic events observed after long-term fenofibrate treatment in humans.

Integrity signals

Registry

Crossref · 10.1016/j.cardiores.2007.03.006

Cites

33 of 33 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

We couldn’t retrieve this paper’s full text, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Blanco-Rivero et al. showed that long term FF treatment in rats induces endothelial dysfunction.

    “Recently Blanco-Rivero et al. [107] showed that long term FF treatment in rats induces endothelial dysfunction.”

    From Fenofibrate and metabolic syndrome (2010) · cites this paper as [107]

Cites

Flagged first, then by citations

1 of the 34 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Related

Authors
BLANCORIVERO, J., MARQUEZRODAS, I., XAVIER, F., ARASLOPEZ, R., ARROYOVILLA, I., FERRER, M., & BALFAGON, G.
Affiliations
  • Universidade Federal de Pernambuco (BR)
  • Universidad Autónoma de Madrid (ES)
ORCID
Venue
Cardiovascular Research
Publisher
Oxford University Press (OUP)
Published
2007-07-15
Volume
75
Issue
2
Pages
398-407
ISSN
0008-6363 (ISSN-L)
DOI
10.1016/j.cardiores.2007.03.006
OpenAlex
W2130306719
Cited by
21
References
34
Citations by year
2023: 1 · 2020: 2 · 2019: 2 · 2015: 2 · 2013: 1 · 2012: 2
FWCI
0.96
Type
journal article
Language
en
Open access
closed
Locations
  • Cardiovascular Research (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
  • Health Sciences › Medicine › Pharmacology › Inflammatory mediators and NSAID effects
Keywords
fenofibrate, endothelium-dependent vasodilation, acetylcholine-induced relaxation, cyclooxygenase pathway, nitric oxide, cyclooxygenase-2, prostacyclin, thromboxane, prostaglandin F2alpha, isoprostanes, endothelial nitric oxide synthase, inducible nitric oxide synthase, aorta, long-term drug treatment, aging, endothelial dysfunction
MeSH terms
Acetylcholine, Animals, Endothelium, Vascular, Indomethacin, Male, Nitric Oxide, Nitrobenzenes, Fenofibrate, Prostaglandin-Endoperoxide Synthases, Prostaglandins F, Sulfonamides, Time Factors, Vasodilation, Vasodilator Agents, Blotting, Western, Dinoprostone, Cyclooxygenase Inhibitors, Rats, Wistar, Rats, Cyclooxygenase 1, Cyclooxygenase 2, Cyclooxygenase 2 Inhibitors, Nitric Oxide Synthase Type II, Nitric Oxide Synthase Type III, In Vitro Techniques

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review