Role of superoxide anions in the mediation of endothelium-dependent contractions

Francesco Cosentino, J. Christopher Sill, Zvonimir S. Katušić

Research output: Contribution to journalArticle

150 Scopus citations

Abstract

We designed experiments to characterize the role of superoxide anions in the mediation of endothelium-dependent contractions in isolated canine basilar arteries. Rings with and without endothelium were suspended for isometric tension recording in Krebs-Ringer bicarbonate solution bubbled with 94% O2-6% CO2 (37°C, pH 7.4). Radioimmunoassay was used to determine the levels of cyclic GMP and cyclic AMP. Calcium ionophore A23187 (10-9 to 10- 6 mol/L) caused concentration-dependent contractions. The removal of endothelium abolished the effect of A23187. Contractions to A23187 were reversed into relaxations in the presence of superoxide dismutase (150 U/mL) or the prostaglandin H2/thromboxane A2 receptor antagonist SQ29548 (10-6 mol/L). N(G)-nitro-L-arginine methyl ester (3 x 10-4 mol/L) augmented contractions to A23187. In rings with endothelium, A23187 (3 x 10-7 mol/L) significantly increased levels of both cyclic AMP and cyclic GMP. Indomethacin (10-5 mol/L) inhibited stimulatory effects of A23187 on cyclic AMP production. In contrast, indomethacin augmented A23187-induced production of cyclic GMP. Selective augmentation of cyclic GMP production by indomethacin appears to be due to protection of nitric oxide or a closely related molecule released following translocation of calcium into endothelial cells. Our findings suggest that (1) an increased concentration of calcium in endothelial cells may activate both cyclooxygenase and the L-arginine/nitric oxide pathway, (2) arachidonic acid metabolism via cyclooxygenase is a source of superoxide anions, and (3) superoxide anions may be responsible for impairment of balance between relaxing and contracting factors leading to contraction of underlying smooth muscle cells.

Original languageEnglish (US)
Pages (from-to)229-235
Number of pages7
JournalHypertension
Volume23
Issue number2
DOIs
StatePublished - Feb 1994

Keywords

  • cerebral arteries
  • free radicals
  • nitric oxide
  • nucleotides, cyclic
  • prostaglandin-endoperoxide synthase

ASJC Scopus subject areas

  • Internal Medicine

Fingerprint Dive into the research topics of 'Role of superoxide anions in the mediation of endothelium-dependent contractions'. Together they form a unique fingerprint.

Cite this