Fellowship for Megan Rhoads: Sympathetic Nerve Activity and T-Lymphocytes in Spontaneously Hypertensive Caribbean Vervets

Title: Sympathetic Nerve Activity and T-lymphocytes in Spontaneously Hypertensive Caribbean Vervets Abstract: (2500 characters) Hypertension is a highly studied disease that contributes to the development of cardiovascular disease and chronic kidney disease, yet rodent models have not elucidated the underlying mechanisms responsible for this pathology. The need exists for an animal model that more closely recapitulates the pathology of human essential hypertension. Chlorocebus aethiops sabaeus, the African Green Monkey or Caribbean vervet, is a novel large animal model that fills this niche. Sympathetic nerve activation and the adaptive immune system have been identified as crucial to the development of essential hypertension, but their interaction has not been studied in a spontaneously hypertensive nonhuman primate model. Aim 1 will determine the effects of á- and â- adrenergic blockade on blood pressure, circulating catecholamines, and T-lymphocyte subpopulations in conscious freely moving spontaneously hypertensive Caribbean vervets. Male and female animals will be implanted with wireless radiotelemetry catheters to capture 24-hour continuous blood pressure, heart rate, electrocardiograph, and core body temperature changes in response to systemic adrenergic receptor (ADR) blockade. ADR antagonists will be infused over a 10-day period testing the hypothesis that systemic adrenergic activation contributes to increased systolic blood pressure in the spontaneously hypertensive Caribbean vervet. Aim 2 will identify the relationships among ADR stimulation and inflammatory cytokine secretion in t-lymphocytes isolated from HT and NT Caribbean vervets. Using in vitro culturing methods, the hypothesis that cultured T-cells isolated from hypertensive animals secrete increased amounts of inflammatory cytokines in response to norepinephrine stimulation will be tested. Aim 1 will present the first documented use of systemic ADR antagonists to lower blood pressure in a freely moving non-human primate model of spontaneous hypertension. Aim 1 will assess how ADR blockade affects circulating norepinephrine and epinephrine concentrations in vivo and how systemic ADR blockade affects circulating t-lymphocyte populations. Aim 2 will clarify the relationship between adrenergic stimulation and the adaptive immune system in the spontaneously hypertensive Caribbean vervet as well as identify the subpopulation of T-lymphocytes responsible for pro-inflammatory cytokine secretion. These experiments will explore how ADR blockade affects cytokine secretion and gene expression of T-lymphocytes in response to catecholamine stimulation. The use of male and female animals in this study will help determine the extent of sexual dimorphism in the development of hypertension in the Caribbean vervet. This proposal will clarify the roles of sympathetic activation and the adaptive immune system in a spontaneous nonhuman primate model of hypertension.