Hypertension, stress, and the kidneys

The National Heart, Lung, and Blood Institute awarded the University of South Carolina $100,228 on December 31, 2026, under the Cardiovascular Diseases Research program (CFDA 93.837) to conduct research on the mechanistic pathways linking hypertension, autoimmunity, and chronic psychological stress.

The research tests whether chronic stress exacerbates immune system activation and hypertension in a female hypertensive mouse model of systemic lupus erythematosus (NZBWF1). The investigator's preliminary data demonstrate that subjecting healthy female mice to a 28-day chronic unpredictable stress protocol increases blood pressure and impairs renal mitochondrial function, and that female NZBWF1 mice with SLE develop hypertension associated with renal mitochondrial dysfunction and autoantibodies to mitochondrial antigens. The central hypothesis is that chronic stress will exacerbate renal mitochondrial dysfunction during SLE, leading to accelerated development of renal disease and hypertension. The work addresses a gap in understanding how chronic stress affects immune activation in patients with autoimmune disorders who have prevalent hypertension.

Performance occurs at Columbia, South Carolina. The award period runs from December 31, 2026, through December 30, 2027. The assistance type is a project grant, a competitive research training award funding basic and translational research in cardiovascular disease prevention and treatment.

Abstract

Hypertension is recognized as a complex disease with autoimmune origins, and chronic psychological stress is associated with hypertension and immune system activation. Patients with autoimmune disorders like systemic lupus erythematosus (SLE) have prevalent hypertension, and disease flares are associated with psychological stress. The mechanistic pathways linking hypertension, autoimmunity, and chronic stress have not been studied. This proposal will directly fill an important knowledge GAP by testing whether chronic stress exacerbates immune system activation and hypertension in an established hypertensive mouse model of SLE (female NZBWF1). My preliminary data show that subjecting healthy female mice (C57BL/6) to a 28-day chronic unpredictable stress (CUS) protocol increases blood pressure and impairs renal mitochondrial function. The females exposed to CUS also have decreased renal progesterone, a SEX steroid that normally preserves mitochondrial function. Published literature suggests that the female NZBWF1 model of SLE displays anxiety-like behaviors as the disease progresses. I have preliminary data affirming that female NZBWF1 mice with SLE develop hypertension, and i have novel data showing that the hypertension is associated with renal mitochondrial function and the presence of autoantibodies to mitochondrial antigens. Based on my data showing that chronic stress causes hypertension, renal mitochondrial dysfunction, and reduced renal progesterone, coupled with data showing that a stress- susceptible mouse model of SLE develops hypertension with impaired renal mitochondrial function, the central hypothesis of this proposal is that chronic stress will exacerbate renal mitochondrial dysfunction during SLE leading to accelerated development of renal disease and hypertension. Aim 1 of the proposal will test the hypothesis that chronic stress superimposed onto autoimmune disease will exacerbate SLE associated hypertension and renal mitochondrial dysfunction. Aim 2 will test the hypothesis that renal mitochondrial dysfunction is an important mechanism for SLE mediated hypertension and is exacerbated by chronic stress. The proposed studies will utilize a rigorous experimental design with state-of-the-art physiological, molecular, and biochemical approaches to identify novel mechanisms underlying stress-related changes in autoimmune mediated hypertension. The proposed studies will also provide direct evidence of the impact of chronic stress on SLE disease progression, which has historically only been reported based on associations.