Type 2 diabetic mice have increased arteriolar tone and blood pressure

Enhanced release of COX-2-derived constrictor prostaglandins

Zsolt Bagi, Nora Erdei, Attila Toth, Wei Li, Thomas H. Hintze, Akos Koller, Gabor Kaley

Research output: Contribution to journalArticle

108 Citations (Scopus)

Abstract

Objective - Type 2 diabetes mellitus (T2-DM) is frequently associated with vascular dysfunction and elevated blood pressure, yet the underlying mechanisms are not completely understood. We hypothesized that in T2-DM, the regulation of peripheral vascular resistance is altered because of changes in local vasomotor mechanisms. Methods and Results - In mice with T2-DM (C57BL/KsJ-db - /db + ), systolic and mean arterial pressures measured by the tail cuff method were significantly elevated compared with those of control (db + /db - ) animals (db/db, 146±5 and 106±2 mm Hg versus control, 133±4 and 98±4 mm Hg, respectively; P<0.05). Total peripheral resistance, calculated from cardiac output values (measured by echocardiography) and mean arterial pressure were significantly elevated in db/db mice (db/db, 25±6 versus control, 15±1 mm Hg[middot]mL -1 [middot]min -1 ). In isolated, pressurized gracilis muscle arterioles (diameter ≈80 μm) from db/db mice, stepwise increases in intraluminal pressure (from 20 to 120 mm Hg) elicited a greater reduction in diameter than in control vessels at each pressure step (at 80 mm Hg, db/db, 66±4% versus control, 79±3%). The passive diameters of arterioles (obtained in Ca 2+ -free solution) and the calculated myogenic index were not significantly different in the 2 groups. The presence of the prostaglandin H 2 /thromboxane A 2 receptor antagonist SQ29548 did not affect arteriolar diameters of control mice but reduced the enhanced arteriolar tone of db/db mice back to control levels (at 80 mm Hg, 80±4%). The inhibitor of cyclooxygenase-1 (COX-1), SC-560, did not affect the basal tone of arterioles, whereas NS-398, an inhibitor of COX-2, caused a significant shift in the arteriolar pressure-diameter curve of vessels from db/db mice (at 80 mm Hg, 76±3%) but not in those of control mice. Also, in aortas of db/db mice, expression of COX-2 was enhanced compared with controls. Conclusions -Collectively, these findings suggest that in mice with T2-DM, the basal tone of skeletal muscle arterioles is increased because of an enhanced COX-2-dependent production of constrictor prostaglandins. These alterations in microvascular prostaglandin synthesis may contribute to the increase in peripheral resistance and blood pressure in T2-DM.

Original languageEnglish (US)
Pages (from-to)1610-1616
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume25
Issue number8
DOIs
StatePublished - Aug 1 2005
Externally publishedYes

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Prostaglandins
Blood Pressure
Type 2 Diabetes Mellitus
Arterioles
Vascular Resistance
Pressure
Arterial Pressure
Prostaglandins H
Cyclooxygenase 1
Cyclooxygenase 2 Inhibitors
Thromboxanes
varespladib methyl
Cardiac Output
Blood Vessels
Echocardiography
Aorta
Tail
Skeletal Muscle

Keywords

  • Basal arteriolar tone
  • Cyclooxygenase-2
  • Microvessels
  • Type 2 diabetes mellitus

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Type 2 diabetic mice have increased arteriolar tone and blood pressure : Enhanced release of COX-2-derived constrictor prostaglandins. / Bagi, Zsolt; Erdei, Nora; Toth, Attila; Li, Wei; Hintze, Thomas H.; Koller, Akos; Kaley, Gabor.

In: Arteriosclerosis, thrombosis, and vascular biology, Vol. 25, No. 8, 01.08.2005, p. 1610-1616.

Research output: Contribution to journalArticle

Bagi, Zsolt ; Erdei, Nora ; Toth, Attila ; Li, Wei ; Hintze, Thomas H. ; Koller, Akos ; Kaley, Gabor. / Type 2 diabetic mice have increased arteriolar tone and blood pressure : Enhanced release of COX-2-derived constrictor prostaglandins. In: Arteriosclerosis, thrombosis, and vascular biology. 2005 ; Vol. 25, No. 8. pp. 1610-1616.
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abstract = "Objective - Type 2 diabetes mellitus (T2-DM) is frequently associated with vascular dysfunction and elevated blood pressure, yet the underlying mechanisms are not completely understood. We hypothesized that in T2-DM, the regulation of peripheral vascular resistance is altered because of changes in local vasomotor mechanisms. Methods and Results - In mice with T2-DM (C57BL/KsJ-db - /db + ), systolic and mean arterial pressures measured by the tail cuff method were significantly elevated compared with those of control (db + /db - ) animals (db/db, 146±5 and 106±2 mm Hg versus control, 133±4 and 98±4 mm Hg, respectively; P<0.05). Total peripheral resistance, calculated from cardiac output values (measured by echocardiography) and mean arterial pressure were significantly elevated in db/db mice (db/db, 25±6 versus control, 15±1 mm Hg[middot]mL -1 [middot]min -1 ). In isolated, pressurized gracilis muscle arterioles (diameter ≈80 μm) from db/db mice, stepwise increases in intraluminal pressure (from 20 to 120 mm Hg) elicited a greater reduction in diameter than in control vessels at each pressure step (at 80 mm Hg, db/db, 66±4{\%} versus control, 79±3{\%}). The passive diameters of arterioles (obtained in Ca 2+ -free solution) and the calculated myogenic index were not significantly different in the 2 groups. The presence of the prostaglandin H 2 /thromboxane A 2 receptor antagonist SQ29548 did not affect arteriolar diameters of control mice but reduced the enhanced arteriolar tone of db/db mice back to control levels (at 80 mm Hg, 80±4{\%}). The inhibitor of cyclooxygenase-1 (COX-1), SC-560, did not affect the basal tone of arterioles, whereas NS-398, an inhibitor of COX-2, caused a significant shift in the arteriolar pressure-diameter curve of vessels from db/db mice (at 80 mm Hg, 76±3{\%}) but not in those of control mice. Also, in aortas of db/db mice, expression of COX-2 was enhanced compared with controls. Conclusions -Collectively, these findings suggest that in mice with T2-DM, the basal tone of skeletal muscle arterioles is increased because of an enhanced COX-2-dependent production of constrictor prostaglandins. These alterations in microvascular prostaglandin synthesis may contribute to the increase in peripheral resistance and blood pressure in T2-DM.",
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T1 - Type 2 diabetic mice have increased arteriolar tone and blood pressure

T2 - Enhanced release of COX-2-derived constrictor prostaglandins

AU - Bagi, Zsolt

AU - Erdei, Nora

AU - Toth, Attila

AU - Li, Wei

AU - Hintze, Thomas H.

AU - Koller, Akos

AU - Kaley, Gabor

PY - 2005/8/1

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N2 - Objective - Type 2 diabetes mellitus (T2-DM) is frequently associated with vascular dysfunction and elevated blood pressure, yet the underlying mechanisms are not completely understood. We hypothesized that in T2-DM, the regulation of peripheral vascular resistance is altered because of changes in local vasomotor mechanisms. Methods and Results - In mice with T2-DM (C57BL/KsJ-db - /db + ), systolic and mean arterial pressures measured by the tail cuff method were significantly elevated compared with those of control (db + /db - ) animals (db/db, 146±5 and 106±2 mm Hg versus control, 133±4 and 98±4 mm Hg, respectively; P<0.05). Total peripheral resistance, calculated from cardiac output values (measured by echocardiography) and mean arterial pressure were significantly elevated in db/db mice (db/db, 25±6 versus control, 15±1 mm Hg[middot]mL -1 [middot]min -1 ). In isolated, pressurized gracilis muscle arterioles (diameter ≈80 μm) from db/db mice, stepwise increases in intraluminal pressure (from 20 to 120 mm Hg) elicited a greater reduction in diameter than in control vessels at each pressure step (at 80 mm Hg, db/db, 66±4% versus control, 79±3%). The passive diameters of arterioles (obtained in Ca 2+ -free solution) and the calculated myogenic index were not significantly different in the 2 groups. The presence of the prostaglandin H 2 /thromboxane A 2 receptor antagonist SQ29548 did not affect arteriolar diameters of control mice but reduced the enhanced arteriolar tone of db/db mice back to control levels (at 80 mm Hg, 80±4%). The inhibitor of cyclooxygenase-1 (COX-1), SC-560, did not affect the basal tone of arterioles, whereas NS-398, an inhibitor of COX-2, caused a significant shift in the arteriolar pressure-diameter curve of vessels from db/db mice (at 80 mm Hg, 76±3%) but not in those of control mice. Also, in aortas of db/db mice, expression of COX-2 was enhanced compared with controls. Conclusions -Collectively, these findings suggest that in mice with T2-DM, the basal tone of skeletal muscle arterioles is increased because of an enhanced COX-2-dependent production of constrictor prostaglandins. These alterations in microvascular prostaglandin synthesis may contribute to the increase in peripheral resistance and blood pressure in T2-DM.

AB - Objective - Type 2 diabetes mellitus (T2-DM) is frequently associated with vascular dysfunction and elevated blood pressure, yet the underlying mechanisms are not completely understood. We hypothesized that in T2-DM, the regulation of peripheral vascular resistance is altered because of changes in local vasomotor mechanisms. Methods and Results - In mice with T2-DM (C57BL/KsJ-db - /db + ), systolic and mean arterial pressures measured by the tail cuff method were significantly elevated compared with those of control (db + /db - ) animals (db/db, 146±5 and 106±2 mm Hg versus control, 133±4 and 98±4 mm Hg, respectively; P<0.05). Total peripheral resistance, calculated from cardiac output values (measured by echocardiography) and mean arterial pressure were significantly elevated in db/db mice (db/db, 25±6 versus control, 15±1 mm Hg[middot]mL -1 [middot]min -1 ). In isolated, pressurized gracilis muscle arterioles (diameter ≈80 μm) from db/db mice, stepwise increases in intraluminal pressure (from 20 to 120 mm Hg) elicited a greater reduction in diameter than in control vessels at each pressure step (at 80 mm Hg, db/db, 66±4% versus control, 79±3%). The passive diameters of arterioles (obtained in Ca 2+ -free solution) and the calculated myogenic index were not significantly different in the 2 groups. The presence of the prostaglandin H 2 /thromboxane A 2 receptor antagonist SQ29548 did not affect arteriolar diameters of control mice but reduced the enhanced arteriolar tone of db/db mice back to control levels (at 80 mm Hg, 80±4%). The inhibitor of cyclooxygenase-1 (COX-1), SC-560, did not affect the basal tone of arterioles, whereas NS-398, an inhibitor of COX-2, caused a significant shift in the arteriolar pressure-diameter curve of vessels from db/db mice (at 80 mm Hg, 76±3%) but not in those of control mice. Also, in aortas of db/db mice, expression of COX-2 was enhanced compared with controls. Conclusions -Collectively, these findings suggest that in mice with T2-DM, the basal tone of skeletal muscle arterioles is increased because of an enhanced COX-2-dependent production of constrictor prostaglandins. These alterations in microvascular prostaglandin synthesis may contribute to the increase in peripheral resistance and blood pressure in T2-DM.

KW - Basal arteriolar tone

KW - Cyclooxygenase-2

KW - Microvessels

KW - Type 2 diabetes mellitus

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