Harry Goldblatt (1891-1977): Pathologist and Medical Researcher.

Harry Goldblatt (1891-1977) was an American pathologist whose research and experiments on renovascular hypertension were an important contribution to understanding and treating this disease. His life and his legacy are discussed in this paper.

John Loesch, discoverer of renovascular hypertension, and Harry Goldblatt: two great pioneers in circulation research.

In 1934, Harry Goldblatt and colleagues published an article titled "The Production of Persistent Elevation of Systolic Blood Pressure by Means of Renal Ischemia" in the Journal of Experimental Medicine. One year earlier, John Loesch had published a similar study in a German-language journal, Zentralblatt für Innere Medizin. His article appeared on 18 and 25 February 1933, in 3 parts, under the title "A Contribution to Experimental Nephritis and to Arterial Hypertension." The central proposition of both papers was the same: Renal ischemia causes persistent hypertension. Goldblatt's article is one of the best known in the history of medicine, and the words "Goldblatt kidney" are still commonly used. Although Loesch succeeded in producing persistent hypertension by inducing ischemia and in correctly interpreting this and its ramifications earlier than Goldblatt, his article has been cited only a few times. In this article, the authors share what is known about the studies of Loesch and of Goldblatt. They believe that both Loesch and Goldblatt should receive equal credit for these important first observations.

On the central role of studies on the kidney in the recognition, conceptual evolution, and understanding of hypertension.

Elevated arterial pressure had long been surmised from the strength of the pulse. Its association with contracted kidneys and hypertrophied hearts was described by Richard Bright (1789-1858). Microscopic observations of the narrowed and obliterated vasculature initially observed in the kidneys of Bright's disease, and subsequently throughout the body, launched clinical research into hypertension. The description of these findings in the absence of symptoms of kidney disease led to the recognition of primary hypertension. Ultimately, the systematic recording of the blood pressure with a pneumatic cuff and mercury manometer established the significance of hypertension as a distinct disease entity. Subsequent experimental studies established the central role of the kidney in hypertension through the renin-angiotensin system and extracellular volume control. This finding provided the basis for the introduction of diuretics and angiotensin converting enzyme inhibitors, two of the most important and valuable antihypertertensive drugs now available. Thus, the study of kidney disease and function has played a pivotal role in the conceptual evolution of the understanding of hypertension as a disease, the identification of its mechanisms, and the development of clinically useful antihypertensive medications.

[Historical Archives of Italian Nephrology. Goldblatt, kidney and hypertension: three steps in the history of nephrology]. / Archivi storici della Nefrologia Italiana.Goldblatt, rene e ipertensione: un trinomio epico nella storia della nefrologia.

The existence of a clear relationship between renal ischemia and hypertension has been widely documented by Harry Goldblatt and his colleagues. In their original papers they showed that gross and persistent elevation of systolic blood pressure could be produced in dogs by clamping both renal artery, or one if the other kidney had been removed. If renal arteries constriction was not too severe, a stable hypertension unaccompanied by more than mild renal impairment was produced. Subsequently, Goldblatt showed that, with severe constriction, retinal changes, arteriolar impairment and left ventricular hypertension could occur. Goldblatt has remained steadily of the opinion that essential hypertension in man is similarly due to renal ischemia occasioned either by stenosis of a main artery, or by organic changes in the smaller renal arteries down to the size of the different glomerular arteries. At first sight, it might seem like a simple matter to correctly identify the chain of events that begins with renal artery constriction and ends with persistent hypertension. Observing that a link was missing in this chain of events, Goldblatt hypothesised that the link was a humoral mechanism. Tigersted and Bergman showed that renin was the missing link. Renal ischemia as cause of hypertension in dogs opened a new chapter in the connection between kidney circulation and blood pressure elevation. This quite unexpected connection is one of the most challenging issues today and clearly demonstrates that the development of Goldblatt's ideas on renal circulation is still important and has by no means ended. Goldblatt, in his epistemologic approach to hypertension scientific challenges, realised that ideas are the building blocks of science: not flights of fancy, not notions sculpted in snow, but enduring concepts. Goldblatt's lasting ideas are more than a function of time and place: they have inherent qualities that have survived up to the present day.

Development of ideas on renovascular hypertension.

Stephen Hales was the first to measure blood pressure directly in the horse (1733), and the definitive studies on human nephrins by Richard Bright followed much later (1836). The relation between high blood pressure and renal disease was established by Mahomed (1872). The discovery of renin and its possible link with Bright's disease was made by Tigerstedt and Bergman (1898), but only the experimental production of renal hypertension by Goldblatt and his colleagues (1934) led to the delineation of the role of the kidney in human hypertension by a wide variety of methods.

Franz Volhard and his students' tortuous road to renovascular hypertension.

Franz Volhard and his students' tortuous road to renovascular hypertension. Harry Goldblatt's name is irrevocably linked to the phenomenon that renal artery constriction increases blood pressure via renin release, even in the absence of significantly decreased renal function. However, "getting there was more than half the fun." A lively competition took place earlier in this century elucidating the role of the kidney in hypertension, in which Franz Volhard and his disciples played a major role. I have reviewed the extensive German literature of the time, and observed that Franz Volhard and his young associates made major contributions investigating decreases in renal perfusion and resultant increases in blood pressure. Hessel, Hartwich, and Volhard made seminal observations in this regard that even preceded those of Goldblatt. A sojourn into this past history gives a revealing insight into our cumulative-albeit still incomplete-knowledge of the kidney, renin-angiotensin system, and blood pressure regulation. Franz Volhard was a colorful figure whose contributions extended far beyond classifying renal diseases.

David M. Hume memorial lecture. Surgical treatment of renovascular hypertension.

BACKGROUND: Renal artery occlusive disease is the most common form of surgically correctable hypertension. Considerable scientific advances have improved our understanding of the pathophysiologic sequellae of a renal artery stenosis, the means of documenting the functional importance of such lesions, and the role of alternative surgical approaches in treating this disease. This work assesses the historical basis for the surgical treatment of renovascular hypertension. DATA SOURCES: A review of the American literature on the subject of renovascular hypertension was undertaken, with particular attention to early work emanating from the University of California, San Francisco, the University of Michigan, and Vanderbilt University. These three institutions had considerable influence on the evolving techniques of operative intervention for renovascular hypertension. CONCLUSIONS: The contemporary surgical management of renal artery stenotic disease causing secondary hypertension includes recognition of the heterogeneic character renal artery diseases, documentation of the functional significance of the stenoses, and performance of a properly chosen operation. Surgical therapy benefits 85% to 95% of properly selected patients having renovascular hypertension.

Franz Volhard Lecture. Evolution of the medullipin concept of blood pressure control: a tribute to Eric Muirhead.

THE HYPOTHESIS: The medullipin system discovered by the late Eric E. Muirhead is a feedback blood-pressure control system operating from the renal medulla. In contrast to the renin-angiotensin system, which upregulates pressure, the medullipin system downregulates blood pressure. THE MECHANISM: A rise in arterial pressure has two important consequences. First, medullary blood flow increases, renal interstitial fluid pressure rises and there is a reduction in the medullary urea osmotic gradient. Second, secretion of medullipin I is increased, which circulates to the liver, where it is converted to the active hormone, medullipin II, by a P-450 cytochrome oxidase pathway. Both of these mechanisms work in parallel to reduce arterial pressure with an increase in the urinary excretion of sodium and water coupled with systemic arterial vasodilation by medullipin II.