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Diastolic Dysfunction in Rats Following Intravenous Injection of HIV gp120
Author(s) -
Chen Fangping,
Berzingi Chalak,
Huang Aijie,
Finkel Mitchell s
Publication year - 2009
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.23.1_supplement.812.9
Subject(s) - lusitropy , diastole , medicine , in vivo , inotrope , hemodynamics , pharmacology , heart failure , p38 mitogen activated protein kinases , cardiomyopathy , cardiology , endocrinology , protein kinase a , phosphorylation , blood pressure , biology , biochemistry , microbiology and biotechnology
HIV infection in patients is associated with a surprisingly high frequency of diastolic dysfunction followed by the development of a dilated cardiomyopathy. Potential mechanisms include direct effects of HIV proteins, including gp120. We have previously reported direct inotropic and signaling effects of HIV gp120 on isolated cardiac myocytes in vitro. We now report effects of a single injection of HIV gp120 on cardiac hemodynamics in vivo. HIV gp120 (50ug/kg) was injected intravenously and hemodynamic measurements were made at 1 hr, 24 hrs and 48 hrs in freely ambulatory, awake rats. Rats injected with gp120 demonstrated a blunted diastolic response to increasing doses of intravenous infusion of the beta‐adrenergic agonist, isoproterenol(ISO), compared with similarly instrumented controls at 48 hrs (gp120 vs control, p<0.01; n=6, for each). Pre‐treatment with the p38 MAP kinase inhibitor, SB 203580, prevented the diastolic dysfunction (gp120+ SB vs control, P=NS; n=6, for each). Western analyses confirmed the inhibition of p38 MAP kinase by SB in vivo. There were no differences in ISO dose response curves or p38 MAP kinase phosphorylation between gp 120‐treated and control rats at 1 or 24 hrs. (P=NS; n=6, for each). Thus, evidence of diastolic dysfunction is apparent in rats following a single dose of HIV gp120. These findings lend further support to the hypothesis that the HIV virus, itself, may contribute to myocardial dysfunction in HIV infected patients.