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

76 Citations (Scopus)

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)
JournalCirculation Research
Volume99
Issue number5
DOIs
StatePublished - Sep 1 2006
Externally publishedYes

Fingerprint

Arterioles
Cyclooxygenase 2
Prostaglandins
Dilatation
Diabetes Mellitus
Bradykinin
Atrial Appendage
Video Microscopy
Experimental Diabetes Mellitus
Cyclooxygenase 2 Inhibitors
Nitroprusside
Indomethacin
Thoracic Surgery
Blood Vessels
Theoretical Models
Perfusion
Tissue Donors

Keywords

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

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Increased cyclooxygenase-2 expression and prostaglandin-mediated dilation in coronary arterioles of patients with diabetes mellitus. / Szerafin, Tamás; Erdei, Nóra; Fülöp, Tibor; Pasztor, Eniko T.; Édes, István; Koller, Akos; Bagi, Zsolt.

In: Circulation Research, Vol. 99, No. 5, 01.09.2006.

Research output: Contribution to journalArticle

Szerafin, Tamás ; Erdei, Nóra ; Fülöp, Tibor ; Pasztor, Eniko T. ; Édes, István ; Koller, Akos ; Bagi, Zsolt. / Increased cyclooxygenase-2 expression and prostaglandin-mediated dilation in coronary arterioles of patients with diabetes mellitus. In: Circulation Research. 2006 ; Vol. 99, No. 5.
@article{7efe0638ca1f4761a9ff8468a94f72ad,
title = "Increased cyclooxygenase-2 expression and prostaglandin-mediated dilation in coronary arterioles of patients with diabetes mellitus",
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.",
keywords = "Bradykinin, Cyclooxygenase 2, Diabetes mellitus, Endothelium, Human coronary arteriole, Prostacyclin",
author = "Tam{\'a}s Szerafin and N{\'o}ra Erdei and Tibor F{\"u}l{\"o}p and Pasztor, {Eniko T.} and Istv{\'a}n {\'E}des and Akos Koller and Zsolt Bagi",
year = "2006",
month = "9",
day = "1",
doi = "10.1161/01.RES.0000241051.83067.62",
language = "English (US)",
volume = "99",
journal = "Circulation Research",
issn = "0009-7330",
publisher = "Lippincott Williams and Wilkins",
number = "5",

}

TY - JOUR

T1 - Increased cyclooxygenase-2 expression and prostaglandin-mediated dilation in coronary arterioles of patients with diabetes mellitus

AU - Szerafin, Tamás

AU - Erdei, Nóra

AU - Fülöp, Tibor

AU - Pasztor, Eniko T.

AU - Édes, István

AU - Koller, Akos

AU - Bagi, Zsolt

PY - 2006/9/1

Y1 - 2006/9/1

N2 - 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.

AB - 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.

KW - Bradykinin

KW - Cyclooxygenase 2

KW - Diabetes mellitus

KW - Endothelium

KW - Human coronary arteriole

KW - Prostacyclin

UR - http://www.scopus.com/inward/record.url?scp=33748340627&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748340627&partnerID=8YFLogxK

U2 - 10.1161/01.RES.0000241051.83067.62

DO - 10.1161/01.RES.0000241051.83067.62

M3 - Article

VL - 99

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

IS - 5

ER -