Personal and Historical Perspectives in Hypertension Discovery of the Renomedullary System of Blood Pressure Control and Its Hormones

I worked with Arthur Grollman for 3Vi years (and 12 scientific publications) beginning in 1947. Arthur was Chairman of the Department of Experimental Medicine, and I became Chairman of the Department of Pathology at Southwestern Medical School in Dallas. Grollman inoculated me with his concept of a "nonexcretory antihypertensive function of the kidney", "incretory" he termed it. For some time, he insisted that this function was a cortical one, gainsaying a medullary one. However, toward the end of his career, he conceded the cellular source of this function as controversial, quoting our position. Several key experiments in our laboratory pointed toward a renomedullary antihypertensive function. Jerry Stirman (a surgeon), Bennie Brooks, my research assistant for 39 years, and I began by transplanting whole kidneys into dogs with sustained renoprival hypertension. These kidneys lowered the blood pressure of the hypertensive recipients rapidly, despite the maintenance of a fluid load that was not overcome by diuresis-natriuresis. Thus, the antihypertensive effect resulted from a function unrelated to volume depletion — a finding consistent with the incretory concept. Next, I discovered that renoprival hypertension of the dog was potentiated by a mixture of saline intravenously and protein by mouth. This combination caused what became known as "accelerated renoprival hypertension" (blood pressure elevation of 30-40 mm Hg within 3-4 days). Anastomosing the ureter to the inferior vena cava prevented this type of hypertension whereas ureteral ligation did not. A major morphological disparity between the kidneys of these two states was noted. Uretero-caval anastomosis was attended by an intact and hypertrophied renal medulla, and ureteral ligation gave rise to acute hydronephrosis and ischemic-type destruction of the renal papilla (obstructive papillary necrosis). This led me to the view that cells in the renal papilla performed the antihypertensive function.