John Laragh and the renin thesis: creating a paradigm.

Abstract

I first heard from John Laragh when I was a research fellow with Gordon Stokes at Sydney Hospital. My main area of interest was the regulation of renin release from the kidney, and Dr. Laragh had noticed some of my published reports describing the effects on renin of beta blockade and other interventions. Of course I was already aware of John Laragh’s two dramatic observations published in the New England Journal of Medicine.1,2 The first of these was to forever change the landscape of cardiovascular medicine, for John and his group provided evidence that inappropriately high plasma levels of renin in patients with hypertension were associated with an increased risk of myocardial infarction and other outcomes.1 This critical observation was later confirmed by a larger prospective study conducted by Michael Alderman.3 Over time, this discovery became progressively broadened and led to the recognition that excess activity of the renin-angiotensin system is an adverse factor in several forms of cardiovascular and renal disease. The second major finding by the Laragh group was that the efficacy of antihypertensive treatment with a betablocker was largely dependent on the drug’s ability to reduce plasma renin activity.2 This sentinel observation demonstrated that the renin-angiotensin system plays a causative role in blood pressure elevations in a large proportion of patients with hypertension. Based on this discovery, drugs that block the renin-angiotensin system have now become one of the mainstays of hypertension therapy.