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Reversal of Adrenergic Desensitization in Prenatally Stressed Rats by P38 Map Kinase Inhibitor, SB203580
Author(s) -
Chen Fangping,
Kan Hong,
Xie Sherry,
Beto Robert J,
Warden Bradford E,
Jain Abnash C,
Finkel Mitchell S
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.970.14
Subject(s) - desensitization (medicine) , p38 mitogen activated protein kinases , kinase , adrenergic , medicine , endocrinology , protein kinase a , pharmacology , microbiology and biotechnology , biology , receptor
We previously reported a defect in beta adrenergic responsiveness in cardiac myoctes isolated from pre‐natally stressed rats (PS) following restraint stress (R) (PS+R). We now report a reversal of the blunted beta adrenergic responsiveness in PS + R with the P38 MAP kinase inhibitor, SB203580, in vivo. Hemodynamics were measured in awake rats using polyurethane tubing inserted percutaneously into the left ventricle and the right femoral artery. Drugs were administered through a jugular venous catheter. PS + R had a significantly attenuated hemodynamic response to increasing doses of isoproterenol, including a reduction in both positive dp/dt (mmHg/s) max (19291¡À654 vs 14742¡À571, Control vs PS+R, respectively. p<0.05), and negative dp/dt (mmHg/s) max (−14834¡À649 vs −10786¡À482, Control vs PS+R, respectively. p<0.05) (n=8–12). SB 203580 treatment of PS+R for 24 hrs reversed the blunted isoproterenol response (19291¡À654 vs 20715 ¡À 515, and −14834¡À649 vs −15649 ¡À371; Control vs PS+R+SB, respectively. p<0.05) (n=8–12). Thus, continuous activation of P38 MAP kinase appears to be required to maintain myocardial dysfunction in this stress‐induced cardiomyopathy model.