CB, BRANDS The SHR experimental model of human essential hypertension is being used in Projects 1, 2, and 3 to study the mechanisms for DAMP-induced hypertension and vascular and renal dysfunction. Accurate blood pressure measurement is a requirement. The unique expertise of the Core B investigators adds a range of capabilities that move the Animal Core well beyond a simple blood pressure-measuring service. Incorporating electrolyte balance measurements adds depth and richness to interpreting blood pressure, through information such as the pressure natriuresis relationship and transients in blood pressure and sodium excretion at initiation or termination of treatment. Coupling chronic blood flow measurement with blood pressure reveals changes in vascular resistance, which is the actual effector in the regulation of pressure and flow. Flexibility is important because blood pressure will be measured over acute and chronic time frames, will be needed for very large groups of animals, and may need to be accompanied by repeated arterial blood samples in the same animal over a period of days to weeks. Core B is structured to provide the highest degree of quality control and consistency in animal data used across all Projects. The overall goal of Core B is to provide the expertise, materials, and labor to measure and interpret arterial pressure, blood flow, vascular resistance, renal function, and metabolic balance chronically in rats, and to provide the platform for developing new approaches for delivery of experimental compounds or measuring systemic or regional hemodynamics as needed. In addition, Core B will be positioned together with Core C to effectively centralize and coordinate activities that are critical elements of several experiments. One key mechanism for accomplishing this is through the Core B Hub Experiment in Aim 1. That experiment will provide blood and tissue samples to all 3 Projects in coordination with Core C. The Hub Experiment was designed so that Core B would serve as a hard link between the 3 Projects: The chronic blood pressure data and tissue samples will be used by all Projects. A key feature of this approach is that these basic data used by all the projects will come from the exact same animals. In addition to the direct benefits on data collection, analysis, and interpretation, this function of Core B inherently facilitates networking and exchange of ideas and information between all components of the Program Project, over and above what they already are doing directly between projects. Thus, through this experiment and other activities, Core B as a whole indeed serves as a hub that is critical to all 3 spokes (Projects) in this PPG.
CB, BRANDS The unifying hypothesis of this program project centers on the role played by damage-associated molecular patterns (DAMPS) in hypertension. The overall goal of Core B is to provide the expertise, materials, and labor to measure and interpret arterial pressure, blood flow, vascular resistance, renal function, and metabolic balance chronically in rats, and to provide the platform for developing new approaches for delivery of experimental compounds or measuring systemic or regional hemodynamics as needed. This will facilitate the scientific endeavors of the projects to discover new mechanisms for the cause and treatment of hypertension.
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