Blood Pressure, Renal Hemodynamics, and Inflammation

University Of Mississippi Med Ctr, Jackson MS

Investigators

Linked publications & trials

Abstract

The incidence of hypertension and vascular dysfunction is high in women with systemic lupus[unreadable] erythematosus (SLE). Inflammatory cytokines are increased during SLE and growing evidence suggests[unreadable] that cytokines can promote hypertension. One possible mechanism by which chronic inflammation may[unreadable] cause SLE hypertension is through impairment of renal function mediated by increased oxidative stress and[unreadable] vascular dysfunction. This may be exacerbated by a reduced expression of PPARgamma in the kidney.[unreadable] PPARgamma is a nuclear transcription factor that has anti-inflammatory and antioxidant affects. Our[unreadable] preliminary data indicates that renal PPARgamma expression is reduced in a mouse model of SLE[unreadable] (NZBWF1); however, its role in SLE hypertension is not clear. The central hypothesis of the currently[unreadable] funded RO1 is that during SLE, inflammatory cytokines TNFalpha and IL-6, and reduced expression of[unreadable] PPARgamma promote oxidative stress leading to endothelial dysfunction. This leads to increased renal[unreadable] vascular resistance and hypertension. This hypothesis is being tested in the following specific aims. 1) To[unreadable] test whether increased RVR and an impaired renal pressure natriuresis relationship contributes to SLE[unreadable] hypertension. 2) To test whether TNFalpha and IL-6 are mediators of impaired renal hemodynamics,[unreadable] tubular function, and hypertension during SLE. 3) To test whether oxidative stress contributes to impaired[unreadable] renal hemodynamics and hypertension during SLE. 4) To test whether reduced renal PPARgamma is an[unreadable] important underlying mechanism contributing to SLE hypertension. Recent data from our laboratory also[unreadable] shows that this model of SLE has visceral obesity and increased circulating levels of the cytokine leptin.[unreadable] Evidence suggests that leptin is important for increased blood pressure during obesity through sympathetic[unreadable] nerve activation, and that individuals with SLE have increased circulating levels of leptin. Therefore, in a[unreadable] new aim, we propose to test the hypothesis that elevated leptin during SLE increases sympathetic nerve[unreadable] activity as another contributing mechanism to SLE hypertension. This career development award will[unreadable] provide additional time at a critical point in my career development that will allow me to expand my research[unreadable] program into this new and exciting area.