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John H. Laragh, MD: clinician-scientist.

Sealey JE - Am. J. Hypertens. (2014)

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Weill Cornell Medical College, New York. jsealey@med.cornell.edu.

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John Laragh is an outstanding clinician-scientist who discovered that renin, a mostly forgotten kidney hormone, causes essential hypertension and its complications... This discovery led to two new classes of drugs, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, which revolutionized the treatment of hypertension, cardiovascular disease, diabetes, and kidney disease and improved innumerable lives... Although he trained as a cardiologist, his studies were often endocrine in nature but based in nephrology... He became chief of nephrology at Columbia College of Physicians & Surgeons, and then chief of cardiology at Weill Cornell Medical College where he founded the Cardiovascular Center... Stanley had developed a double isotope dilution method for measuring aldosterone in which synthetic aldosterone was tritiated, purified, and injected into the patient; a 24-hour urine was collected; a urinary metabolite was purified, acetylated with carbon 14, and repurified; and after 3–5 weeks of intensive work, aldosterone secretion was calculated from the tritium/carbon 14 ratio... Using this laborious method, they found that aldosterone is not abnormally high in most hypertensive patients... The fact that malignant hypertensive patients all had severe kidney disease led him to Harry Goldblatt’s work... He decided to test the effect of renin, as well as other vasoactive substances, on aldosterone secretion... This led Laragh to his volume-vasoconstriction hypothesis (Figure 1), in which he proposed that dual mechanisms are responsible for the pathophysiology of hypertension: (i) an excess of body sodium-volume in low renin patients and (ii) plasma renin levels that are too high for the current body sodium-volume content in medium to high renin patients... His observation that all effective antihypertensive drugs are either natriuretic (anti-V) or block or suppress the activity of the renin-angiotensin system (anti-R) supported this hypothesis... John’s discovery that hypertension could be controlled by blocking the renin-angiotensin system with an intravenous extract of snake venom that stopped the conversion of Ang I to Ang II was a major breakthrough... It led the pharmaceutical industry to develop orally active angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, thereby revolutionizing the treatment of hypertension and its complications... This led his group to compare outcomes in low, medium, and high renin essential hypertensive patients... They found that the high renin hypertensives die sooner of heart attacks and strokes than those who have low renin and equivalent or even higher elevations in blood pressure... Patients with medium to high PRA levels are given drugs that block or suppress renin-angiotensin system activity, whereas natriuretic drugs are reserved for those with either suppressed or blocked PRA levels.

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John Laragh and Jean Sealey reviewing data (1974).
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Figure 2: John Laragh and Jean Sealey reviewing data (1974).

Mentions: John’s discovery that hypertension could be controlled by blocking the renin-angiotensin system with an intravenous extract of snake venom that stopped the conversion of Ang I to Ang II was a major breakthrough.26 It led the pharmaceutical industry to develop orally active angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, thereby revolutionizing the treatment of hypertension and its complications. In 1975, Time Magazine put John H. Laragh on its cover for this pioneering work (Figure 2).


John H. Laragh, MD: clinician-scientist.

Sealey JE - Am. J. Hypertens. (2014)

John Laragh and Jean Sealey reviewing data (1974).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4125340&req=5

Figure 2: John Laragh and Jean Sealey reviewing data (1974).
Mentions: John’s discovery that hypertension could be controlled by blocking the renin-angiotensin system with an intravenous extract of snake venom that stopped the conversion of Ang I to Ang II was a major breakthrough.26 It led the pharmaceutical industry to develop orally active angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, thereby revolutionizing the treatment of hypertension and its complications. In 1975, Time Magazine put John H. Laragh on its cover for this pioneering work (Figure 2).

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Weill Cornell Medical College, New York. jsealey@med.cornell.edu.

AUTOMATICALLY GENERATED EXCERPT
Please rate it.

John Laragh is an outstanding clinician-scientist who discovered that renin, a mostly forgotten kidney hormone, causes essential hypertension and its complications... This discovery led to two new classes of drugs, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, which revolutionized the treatment of hypertension, cardiovascular disease, diabetes, and kidney disease and improved innumerable lives... Although he trained as a cardiologist, his studies were often endocrine in nature but based in nephrology... He became chief of nephrology at Columbia College of Physicians & Surgeons, and then chief of cardiology at Weill Cornell Medical College where he founded the Cardiovascular Center... Stanley had developed a double isotope dilution method for measuring aldosterone in which synthetic aldosterone was tritiated, purified, and injected into the patient; a 24-hour urine was collected; a urinary metabolite was purified, acetylated with carbon 14, and repurified; and after 3–5 weeks of intensive work, aldosterone secretion was calculated from the tritium/carbon 14 ratio... Using this laborious method, they found that aldosterone is not abnormally high in most hypertensive patients... The fact that malignant hypertensive patients all had severe kidney disease led him to Harry Goldblatt’s work... He decided to test the effect of renin, as well as other vasoactive substances, on aldosterone secretion... This led Laragh to his volume-vasoconstriction hypothesis (Figure 1), in which he proposed that dual mechanisms are responsible for the pathophysiology of hypertension: (i) an excess of body sodium-volume in low renin patients and (ii) plasma renin levels that are too high for the current body sodium-volume content in medium to high renin patients... His observation that all effective antihypertensive drugs are either natriuretic (anti-V) or block or suppress the activity of the renin-angiotensin system (anti-R) supported this hypothesis... John’s discovery that hypertension could be controlled by blocking the renin-angiotensin system with an intravenous extract of snake venom that stopped the conversion of Ang I to Ang II was a major breakthrough... It led the pharmaceutical industry to develop orally active angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, thereby revolutionizing the treatment of hypertension and its complications... This led his group to compare outcomes in low, medium, and high renin essential hypertensive patients... They found that the high renin hypertensives die sooner of heart attacks and strokes than those who have low renin and equivalent or even higher elevations in blood pressure... Patients with medium to high PRA levels are given drugs that block or suppress renin-angiotensin system activity, whereas natriuretic drugs are reserved for those with either suppressed or blocked PRA levels.

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