The renin-angiotensin system (RAS) was extensively investigated and characterized throughout the first half of the 20th century. However, its contribution to the maintenance of high blood pressure (BP) in essential hypertension and to the development of hypertensive cardiac complications remained under debate until the advent of the first pharmacologic probes capable of blocking its actions, namely the angiotensin receptor blocker (ARB) saralasin and the angiotensin-converting enzyme inhibitor (ACEI) teprotide in the early 1970???s. Using these probes, we could demonstrate that even in normal-renin and low-rein hypertension, blockade of the RAS produced a fall in BP. And this fall was maximized if the patient had been previously submitted to sodium depletion by diuretics or low salt diet, which might produce only a small BP fall by itself, but rendered the hypertension RAS-dependent and far more responsible to RAS blockade
