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HIV gp120 induces cardiac dysfunction in vivo associated with p38 MAP kinase phosphorylation and iNOS protein synthesis
Author(s) -
Fang Qiujuan,
kan hong,
xie Sherry,
Finkel Mitchell S
Publication year - 2006
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.20.5.a1196-a
Subject(s) - in vivo , lusitropy , diastole , p38 mitogen activated protein kinases , medicine , nitric oxide , nitric oxide synthase , phosphorylation , kinase , endocrinology , protein kinase a , ex vivo , cardiac function curve , inotrope , pharmacology , biology , heart failure , biochemistry , blood pressure , microbiology and biotechnology
Cardiac dysfunction is a frequently observed consequence of HIV infection. We have previously reported that the addition of gp120 to adult rat ventricular myocytes (ARVM) results in a p38 MAP kinase dependent negative inotropic effect. However, the effect of gp120 on in vivo has not been studied. We now report that HIV gp120 altered cardiac function was associated with activation of P38 MAP kinase and an increase of inducible nitric oxide synthesis in vivo animal model. A single i.v injection of gp120 (50□g/kg) results in both systolic (+dp/dt max = 10279 ± 143 baseline vs 8392 ± 180 at 12 days; N=4) and diastolic (−dp/dt min = 9071 ± 218 at baseline vs 7492 ± 294 at 12 days; N= 4) dysfunction in awake rats. Similarly instrumented, but vehicle injected rats maintained both systolic (+dp/dt max = 10067 ± 360 baseline vs 10468 ± 382 at 12 days; p<.05; N=4) and diastolic (−dp/dt min = 9240 ± 429 baseline vs 9194 ± 321 at 12 days; p<.05; N=4) function. This single injection of gp120 in the awake rat also resulted in a specific decreased diastolic relaxation response to isoproterenol as reflected in smaller −dp/dtmin responses. A single i.v injection of gp120 induced cardiac dysfunction in vivo was associated with p38 MAP kinase phosphorylation and iNOS protein at 48 hrs in adult rat ventricular myocytes. These data suggested that p38 MAP kinase phosphorylation and iNOS protein may contribute to gp120 induced cardiac dysfunction in vivo.