Early Life Stress & Chronic Control of Blood Pressure

Aim 1: To test the hypothesis that adrenergic pathway activation impairs the renal capacity to control blood pressure in response to hypertensive stimuli in adult MS rats through AT1 receptor activation. We will measure renal nerve activity at baseline and in response to chronic AngII. We will determine components of the adrenergic signaling pathways using competitive binding assays, electron microscopy, RT-PCR and western blot. We will use different selective adrenergic agonists and antagonists to elucidate the contribution of the different ARs subtypes. Also, we will block the renin angiotensin system at renal, systemic and central levels to show the impact in the sympathetic outflow to the kidney using in vivo experiments (i.c.v. ionjections, radiotelemetry, renal blood flow, chronic catheter implantation). Aim 2: To test the hypothesis that MS primes blood pressure in response to a HFD through an exaggerated renal and/or adipose tissue adrenergic pathway that influences the AT1 receptor activation. We will study the effect of MS in the programming of the fat tissue. We will study the quantity and quality of the adipose tissue. Measurement of components of the renin angiotensin system using RT-PCR, Western blot and HPLC in adipose tissue will be performed. Also, we will assess the role of the sympathetic tone in MS rats fed a HFD using in vivo experiments involving radiotelemetry and measurement of the metabolic and renal function.