Vascular interleukin-10 protects against LPS-induced vasomotor dysfunction

Carol A Gunnett; Donald D Lund; Frank M Faraci; Donald D Heistad

doi:10.1152/ajpheart.01234.2004

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Vascular interleukin-10 protects against LPS-induced vasomotor dysfunction

Journal article

Peer reviewed

Vascular interleukin-10 protects against LPS-induced vasomotor dysfunction

Carol A Gunnett, Donald D Lund, Frank M Faraci and Donald D Heistad

American journal of physiology. Heart and circulatory physiology, Vol.289(2), pp.H624-630

08/2005

DOI: 10.1152/ajpheart.01234.2004

PMID: 16014616

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Abstract

We tested the hypotheses that 1) systemic IL-10, after adenoviral gene transfer, protects arteries from impaired relaxation produced by LPS; 2) local expression of IL-10 within the arterial wall protects against vasomotor dysfunction after LPS; and 3) IL-10 protects against vascular dysfunction mediated by inducible NO synthase (iNOS) after LPS. In IL-10-deficient (IL-10-/-) and wild-type (WT, IL-10+/+) mice, LPS in vivo impaired relaxation of arteries to acetylcholine and gene transfer of IL-10 improved responses to acetylcholine. Superoxide levels were elevated in arteries after LPS, and increased levels of superoxide were prevented by gene transfer of IL-10. In arteries incubated with a low concentration of LPS in vitro to eliminate systemic effects of LPS and IL-10 from nonvascular sources, responses to acetylcholine were impaired in IL-10-deficient mice and impairment was largely prevented by gene transfer in vitro of IL-10. In arteries from WT mice in vitro, the low concentration of LPS did not impair responses to acetylcholine. Thus IL-10 within the vessel wall protects against LPS-induced dysfunction. In IL-10-deficient mice, aminoguanidine, which inhibits iNOS, protected against vasomotor dysfunction after LPS. In arteries from iNOS-deficient mice, LPS did not impair responses to acetylcholine. These findings suggest that both systemic and local effects of IL-10 provide important protection of arteries against an inflammatory stimulus and that IL-10 decreases iNOS-mediated impairment of vasorelaxation after LPS.

Carotid Arteries - drug effects

Gene Transfer Techniques

Interleukin-10 - deficiency

Vascular Diseases - prevention & control

Vasodilator Agents - pharmacology

Acetylcholine - pharmacology

Humans

Male

Leukocytes - physiology

Cell Adhesion

Nitric Oxide Synthase Type II

Vascular Diseases - chemically induced

Mice, Knockout

Animals

Nitric Oxide Synthase - deficiency

Interleukin-10 - genetics

Lipopolysaccharides - pharmacology

Mice

Nitric Oxide Synthase - metabolism

Vasodilation - drug effects

In Vitro Techniques

Endothelium, Vascular

Interleukin-10 - pharmacology

Details

Title: Subtitle: Vascular interleukin-10 protects against LPS-induced vasomotor dysfunction
Creators: Carol A Gunnett - Department of Internal Medicine, Univ. of Iowa Carver College of Medicine, Iowa City, IA 52242-6778, USA
Donald D Lund
Frank M Faraci
Donald D Heistad
Resource Type: Journal article
Publication Details: American journal of physiology. Heart and circulatory physiology, Vol.289(2), pp.H624-630
Publisher: United States
DOI: 10.1152/ajpheart.01234.2004
PMID: 16014616
ISSN: 0363-6135
eISSN: 1522-1539
Grant note: HL-16066 / NHLBI NIH HHS HL-38901 / NHLBI NIH HHS NS-24621 / NINDS NIH HHS HL-62984 / NHLBI NIH HHS DK-54759 / NIDDK NIH HHS
Language: English
Date published: 08/2005
Academic Unit: Cardiovascular Medicine; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984040545402771

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