Are Local Renin–Angiotensin Systems the Focal Points for Understanding Salt Sensitivity in Hypertension?

  • Edward D. Frohlich
Conference paper


Salt has had a prominent role in the history of man. Initially involving social, economic, and political aspects of human endeavor, in more recent decades salt has become extremely important in its role in the pathogenesis of cardiovascular and renal diseases. The magnitude of this relationship is of tremendous significance, affecting the health of billions of people throughout the world. Our laboratory studies in the adult spontaneously hypertensive rat and in its normotensive control Wistar Kyoto rat over the past 30 to 40 years have clearly demonstrated that in addition to elevating arterial pressure slightly, but significantly, long term salt loading produced severe structural and functional derangements of the vital organs. These salt induced changes have resulted in severe fibrosis (with deposition of hydroxyproline, type 1collagen), ischemia of both ventricles (the hypertrophied left as well as the non-hypertrophied right), and impaired diastolic ventricular function in the presence of preserved systolic function. The aorta demonstrated severe fibrosis and impaired distensibility and pulse wave velocity. Furthermore, the kidneys demonstrated severe changes of nephrosclerosis manifested by marked ischemia, fibrosis, small cell infiltration, glomerular sclerosis, increased total arteriolar resistance associated with afferent and efferent glomerular resistances with increased glomerular hydrostatic pressure, and marked proteinuria. The changes are typical of diastolic functional impairment of the heart and end-stage renal disease in patients with end-stage renal disease that were dramatically prevented and/or reversed by either of two angiotensin II (type 1) receptor blocking agents. These salt induced cardiac, vascular and renal structural and functional findings are strikingly similar to the target organ involvements in patients with essential hypertension associated with suppression of the endocrine rennin–angiotensin system mediated through the juxtaglomerular apparatus, We therefore suggest that these disastrous effects of salt loading are mediated through local cardiac, vascular, and renal angiotensin systems in these organs. They are dramatically supported by a large recent multicenter clinical trial involving prehypertensive patients who were maintained on their usual salt loaded diets and were compared with similar patients who received a salt restricted diet. Further studies are in progress to elaborate this attractive and novel mechanism of action.


Essential Hypertension Salt Sensitivity Salt Loading Diastolic Ventricular Dysfunction Juxtaglomerular Apparatus 
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Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Edward D. Frohlich
    • 1
  1. 1.Ochsner Clinic FoundationNew OrleansUSA

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