Salt sensitivity in response to renal injury requires renal angiotensin-converting enzyme

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.Fil: Giani, Jorge Fernando. Cedars Sinai Medical Center; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bernstein, Kenneth E.. Cedars Sinai Medical Center; Estados UnidosFil: Janjulia, Tea. Cedars Sinai Medical Center; Estados UnidosFil: Han, Jiyang. Keck School Of Medicine Of Usc; . University of Southern California; Estados UnidosFil: Toblli, Jorge Eduardo. Universidad de Buenos Aires; Argentina. Hospital Alemán. Laboratorio de Medicina Experimental; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Shen, Xiao Z.. Cedars Sinai Medical Center; Estados UnidosFil: Rodriguez Iturbe, Bernardo. Cedars Sinai Medical Center; Estados Unidos. Hospital Universitario de Maracaibo; VenezuelaFil: McDonough, Alicia A.. University of Southern California; Estados UnidosFil: Gonzalez Villalobos, Romer A.. Cedars Sinai Medical Center; Estados Unido

Renal angiotensin-converting enzyme is essential for the hypertension induced by nitric oxide synthesis inhibition

The kidney is an important source of angiotensin-converting enzyme (ACE) in many species, including humans. However, the specific effects of local ACE on renal function and, by extension, BP control are not completely understood. We previously showed that mice lacking renal ACE, are resistant to the hypertension induced by angiotensin II infusion. Here, we examined the responses of these mice to the low-systemic angiotensin II hypertensive model of nitric oxide synthesis inhibition with L-NAME. In contrast to wild-type mice, mice without renal ACE did not develop hypertension, had lower renal angiotensin II levels, and enhanced natriuresis in response to L-NAME. During L-NAME treatment, the absence of renal ACE was associated with blunted GFR responses; greater reductions in abundance of proximal tubule Na+/H+ exchanger 3, Na+/Pi co-transporter 2, phosphorylated Na+/K+/Cl- cotransporter, and phosphorylated Na+/Cl- cotransporter; and greater reductions in abundance and processing of the γ isoform of the epithelial Na+ channel. In summary, the presence of ACE in renal tissue facilitates angiotensin II accumulation, GFR reductions, and changes in the expression levels and post-translational modification of sodium transporters that are obligatory for sodium retention and hypertension in response to nitric oxide synthesis inhibition.Fil: Giani, Jorge Fernando. Cedars Sinai Medical Center; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Janjulia, Tea. Cedars Sinai Medical Center; Estados UnidosFil: Kamat, Nikhil. University of Southern California; Estados UnidosFil: Seth, Dale M.. University of Tulane; Estados UnidosFil: Blackwell, Wendell-Lamar B.. Cedars Sinai Medical Center; Estados UnidosFil: Shah, Kandarp H.. Cedars Sinai Medical Center; Estados UnidosFil: Shen, Xiao Z.. Cedars Sinai Medical Center; Estados UnidosFil: Fuchs, Sebastien. Western University of Health Sciences; Estados UnidosFil: Delpire, Eric. Vanderbilt University; Estados UnidosFil: Toblli, Jorge Eduardo. Hospital Aleman; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bernstein, Kenneth E.. Cedars Sinai Medical Center; Estados UnidosFil: McDonough, Alicia A.. University of Southern California; Estados UnidosFil: Gonzalez Villalobos, Romer A.. Cedars Sinai Medical Center; Estados Unido