Enhanced vascular reactivity of small mesenteric arteries from diabetic mice is associated with enhanced oxidative stress and cyclooxygenase products

Malarvannan Pannirselvam, William B. Wiehler, Todd Anderson, Christopher Triggle

Research output: Contribution to journalArticle

68 Citations (Scopus)

Abstract

Vascular reactivity to the alpha-adrenoceptor agonist phenylephrine (PE) was enhanced in small mesenteric arteries (SMA) from diabetic (db/db) mice under both high and low in vitro oxygen conditions. Mechanical removal of the endothelium significantly attenuated the enhanced vascular reactivity of SMA from db/db mice. Acute incubation of the SMA with sepiapterin, a precursor of tetrahydrobiopterin, and N ω-nitro L-arginine (L-NA), an inhibitor of nitric oxide (NO) synthase (NOS), resulted in no significant change in the enhanced vascular reactivity to PE in db/db mice. Endothelial nitric oxide synthase (eNOS) mRNA and protein levels in SMA were not different between db/+ and db/db mice. Acute incubation of SMA with a combination of polyethylene glycol superoxide dismutase and catalase significantly reduced the enhanced contraction to PE in db/db mice. There were higher levels of malondialdehyde, a marker of lipid peroxidation and basal superoxide as measured by dihydroethidium staining, in SMA from db/db mice compared to db/+ mice. Acute incubation with indomethacin, a nonselective inhibitor of cyclooxygenase, SQ 29548, a selective thromboxane receptor antagonist and furegrelate, a thromboxane synthesis inhibitor, significantly attenuated the enhanced contraction to PE in SMA from db/db mice. This study demonstrates that the enhanced contractility of SMA from db/db mice to PE was endothelium dependent and involves elevated reactive oxygen species, cyclooxygenase activity and thromboxane synthesis, but not changes in the eNOS/NO pathway.

Original languageEnglish
Pages (from-to)953-960
Number of pages8
JournalBritish Journal of Pharmacology
Volume144
Issue number7
DOIs
Publication statusPublished - Apr 2005
Externally publishedYes

Fingerprint

Mesenteric Arteries
Prostaglandin-Endoperoxide Synthases
Blood Vessels
Oxidative Stress
Phenylephrine
Nitric Oxide Synthase Type III
Thromboxanes
Endothelium
Thromboxane Receptors
Cyclooxygenase Inhibitors
Malondialdehyde
Nitric Oxide Synthase
Superoxides
Indomethacin
Catalase
Adrenergic Receptors
Lipid Peroxidation
Arginine
Reactive Oxygen Species
Nitric Oxide

Keywords

  • Cyclooxygenase
  • db/db
  • Endothelial nitric oxide synthase
  • Oxidative stress
  • Phenylephrine
  • Small mesenteric arteries
  • Thromboxane

ASJC Scopus subject areas

  • Pharmacology

Cite this

Enhanced vascular reactivity of small mesenteric arteries from diabetic mice is associated with enhanced oxidative stress and cyclooxygenase products. / Pannirselvam, Malarvannan; Wiehler, William B.; Anderson, Todd; Triggle, Christopher.

In: British Journal of Pharmacology, Vol. 144, No. 7, 04.2005, p. 953-960.

Research output: Contribution to journalArticle

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