The ultimate purpose of our research is to analyze the control mechanisms for extracellular fluid volume (ECFV) regulation. To comprehend the regulation of ECFV it is necessary to understand the factors that regulate the ECFV magnitude (namely the body fluid input and output), and the factors that control the distribution of ECFV between the vascular and the interstitial compartments (namely the whole-body transvascular fluid flux and lymph flow). A central hypothesis in these studies is the following: high plasma levels of ANP, at pathophysiological levels, result in an increase in thoracic duct lymph flow, which is due to an increase in whole- body transvascular fluid flux. Experiments are planned to analyze the regulation of ECFV distribution during acute and chronic high plasma levels of atrial natriuretic peptide (ANP). For this we will quantitate the whole-body transvascular fluid flux and lymph flow. Additionally, we plan experiments to evaluate the contribution of the micro-circulatory beds of the skeletal muscle and the subcutaneous tissue to the whole-body transvascular fluid flux and lymph flow during high plasma levels of ANP. Also, the fluid input and fluid output will be quantitated during our experiments, thus the regulators of EVFV magnitude will be studied. An important aspect of these studies is that the plasma levels of ANP will be within the pathophysiological range, are not in the pharmacological range. Therefore, our data will be relevant to pathophysiological states. A major objective of this project is to introduce students to current biomedical research. This experience should be beneficial to students wishing to become clinicians, basic science researchers in academic centers or in the biomedical industry. Our experiments will be performed on conditioned mongrel dogs, which will instrumented with arterial, venous and lymphatic catheters. All data will be collected in conscious (anesthesia-free) animals. Some variables, such as mean arterial pressure, and peripheral lymph flow, will be monitored continuously. All these experiments will provide new information on acute and chronic mechanisms of ECFV regulation. Therefore, this should increase the understanding of pathophysiological states such as edema, cirrhosis, anasarca, congestive heart failure, and arterial hypertension. Finally, we will gain knowledge of the mechanisms of action of the ANP, a hormone that may be manipulated pharmacologically, and this may be of great potential therapeutic use in the practice of medicine.
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