Salt Sensitivity in Response to Renal Injury Requires Renal Angiotensin-Converting Enzyme

Hypertension. 2015 Sep;66(3):534-42. doi: 10.1161/HYPERTENSIONAHA.115.05320. Epub 2015 Jul 6.

Abstract

Recent evidence indicates that salt-sensitive hypertension can result from a subclinical injury that impairs the kidneys' capacity to properly respond to a high-salt diet. However, how this occurs is not well understood. Here, we showed that although previously salt-resistant wild-type mice became salt sensitive after the induction of renal injury with the nitric oxide synthase inhibitor Nω-nitro-l-arginine methyl ester hydrochloride; mice lacking renal angiotensin-converting enzyme, exposed to the same insult, did not become hypertensive when faced with a sodium load. This is because the activity of renal angiotensin-converting enzyme plays a critical role in (1) augmenting the local pool of angiotensin II and (2) the establishment of the antinatriuretic state via modulation of glomerular filtration rate and sodium tubular transport. Thus, this study demonstrates that the presence of renal angiotensin-converting enzyme plays a pivotal role in the development of salt sensitivity in response to renal injury.

Keywords: angiotensin-converting enzyme; diet; glomerular filtration rate; hypertension; inflammation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Kidney Injury / chemically induced
  • Acute Kidney Injury / metabolism*
  • Angiotensin II / metabolism
  • Animals
  • Disease Models, Animal
  • Hypertension / metabolism
  • Kidney / metabolism*
  • Mice
  • Mice, Transgenic
  • NG-Nitroarginine Methyl Ester
  • Peptidyl-Dipeptidase A / genetics
  • Peptidyl-Dipeptidase A / metabolism*
  • Sodium Chloride, Dietary*

Substances

  • Sodium Chloride, Dietary
  • Angiotensin II
  • Peptidyl-Dipeptidase A
  • NG-Nitroarginine Methyl Ester