gms | German Medical Science

27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga

Deutsche Liga zur Bekämpfung des hohen Blutdrucks – Deutsche Hypertonie Gesellschaft e. V.

26. bis 29.11.2003, Bonn

Reduction of heart failure in streptozotocin-induced diabetic rats after p38 MAPK inhibition

Verminderung der Diabetes-mellitus-bedingten Herzinsuffizienz nach Inhibition der p38 MAP-Kinase

Meeting Abstract (Hypertonie 2003)

Suche in Medline nach

  • presenting/speaker D.C. Unger - Charite-Universitätsmedizin Berlin (Berlin, D)
  • C.T. Tschöpe - Charite-Universitätsmedizin Berlin (Berlin, D)

Hypertonie 2003. 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga. Bonn, 26.-29.11.2003. Düsseldorf, Köln: German Medical Science; 2004. Doc03hochP67

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Veröffentlicht: 11. November 2004

© 2004 Unger et al.
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p38 Mitogen-activated protein kinase (p38 MAPK) is one of the most ancient intracellular signaling molecules and is involved in multiple cellular processes, including cell growth, cell proliferation and apoptosis.

Many factors/stresses are known to activate the p38 MAPK. One of them is hyperglycemia.

In the heart, enhanced activation of p38 MAPK is associated with ischemia and/or reperfusion injury and the onset of heart failure.

To investigate the possible functional role of p38 MAPK during the development of diabetes mellitus-induced heart failure we measured cardiac/haemodynamic parameters in streptozotocin (STZ) induced diabetic rats treated with the selective p38 MAPK inhibitor (p38-I) SB 239063.

Experiments were performed in STZ-induced diabetic Sprague Dawley (SD) rats treated with p38-I (70mg/kg/day;p.o.) or vehicle and in age matched controls (n=9/group).

6 weeks after STZ injection haemodynamic parameters for systolic (LVP, dP/dtmax) and diastolic function (LVEDP, dP/dtmin, Tau) and HR were studied in anaesthetized animals using a 2F Millar-tip-catheter inserted in the left ventricle via the right carotid artery.

LV function between normoglycemic SD and SD/p38-I did not differ. As expected SD/STZ animals developed an impaired LV function indicated by a reduction in LVP (64.6±1.7 vs. 101.3±1.7; [mmHg], p<0.05) and dP/dtmax (2606.18±228.1 vs. 4373.33±162;[mmHg/sec], p<0.05) as well as an increase in dP/dtmin (-1998.74±159.1 vs. -3900.1±121.7;[mmHg/sec], p<0.05), Tau (22.8±2.2 vs. 14.9±0.7;[ms], p<0.05) and LVEDP (9.88±0.7 vs. 4.02±0.4; [mmHg], p<0.05) compared to normoglycemic controls.

LV function of SD/STZ/p38-I rats was significantly improved compared to SD/STZ animals (LVP 75.7±1.8; dP/dtmax 3626.9±176; dP/dtmin -2931±126; Tau 18.7±1.4).

Thus, we conclude that inhibition of p38 MAPK may provide a protective effect for the heart under STZ-diabetic conditions.