Increased cyclooxygenase-2 expression and prostaglandin-mediated dilation in coronary arterioles of patients with diabetes mellitus

Tamás Szerafin, Nóra Erdei, Tibor Fülöp, Eniko T. Pasztor, István Édes, Akos Koller, Zsolt Bagi

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Based on findings of experimental models of diabetes mellitus (DM) showing increased expression of vascular cyclooxygenase-2 (COX-2), we hypothesized that in patients with DM changes in COX-2-dependent prostaglandin synthesis affect vasomotor responses of coronary arterioles. Arterioles were dissected from the right atrial appendages obtained at the time of cardiac surgery of patient with DM(+) or without documented diabetes DM(-). Isolated arterioles (89±15 μm in diameter) were cannulated and pressurized (at 80 mm Hg), and changes in diameter were measured with video microscopy. After spontaneous tone developed [DM(-): 32±7%; DM(+): 37±5%; P=NS], arteriolar responses to bradykinin were investigated. Dilations to bradykinin (0.1 nmol/L to 1 μmol/L) were significantly (P<0.05) greater in DM(+) than DM(-) patients (10 nmol/L: 77±10% versus 38±14%). In both groups, dilations were similar to the NO-donor, sodium nitroprusside. In arterioles of DM(+), but not those of DM(-), patients' bradykinin-induced dilations were reduced by the nonselective COX inhibitor indomethacin or by the selective COX-2 inhibitor NS-398 (DM(+) at 10 nmol/L: to 20±4% and 29±7%, respectively). Correspondingly, a marked COX-2 immunostaining was detected in coronary arterioles of DM(+), but not in those of DM(-) patients. We conclude that in coronary arterioles of diabetic patients bradykinin induces enhanced COX-2-derived prostaglandin-mediated dilation. These findings are the first to show that in humans diabetes mellitus increases COX-2 expression and dilator prostaglandin synthesis in coronary arterioles, which may serve to increase dilator capacity and maintain adequate perfusion of cardiac tissues.

Original languageEnglish (US)
Pages (from-to)e12-e17
JournalCirculation research
Volume99
Issue number5
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

Keywords

  • Bradykinin
  • Cyclooxygenase 2
  • Diabetes mellitus
  • Endothelium
  • Human coronary arteriole
  • Prostacyclin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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