Studies conducted in the Principal Investigator's laboratory under this grant support have yielded several important insights into the mechanisms underlying progression of glomerular injury: 1) Structural deterioration of glomeruli occurs under the influence of growth stimuli, 2) circulating substance(s) or 'uremic toxin(s)' appear to promote these stimuli, 3) certain vasoconstrictors participate not only in the abnormal glomerular hemodynamics, which underlie overt proteinuria, but also contribute to structural deterioration, 4) angiotensin II appears to be an important contributor to these processes of glomerular growth and damages. The 5-year grant has enabled this laboratory to develop several new methodologies, which were the key to the success of our studies: 1) Repeated micropuncture measurements within the same nephron over time, 2) three-dimensional glomerular structural analysis, 3) chronic dialysis of rodents. Under this grant support our research has also been extended into human study. Our studies together with the evolution of the general interest apparent in the literature led us to recognize that to attain the next level of understanding requires application of the newest biochemical and molecular biological technologies. In this renewal proposal, we aim to employ some of these newest technologies to delineate the biological actions of angiotensin II which are finked to glomerular (and renal) growth and evolution of disease.
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