title: Renal cortical vasoconstriction contributes to development of salt-sensitive hypertension after angiotensin II exposure.
abstract: Rats that are administered angiotensin II (AngII) for 2 wk develop persistent salt-sensitive hypertension, which can be prevented by the immunosuppressor mycophenolate mofetil (MMF) given during the AngII infusion. This study examined the contribution of glomerular hemodynamics (GFR dynamics) in the post-AngII hypertensive response to a high-salt diet (HSD) and the effect of MMF treatment. During AngII administration, rats developed severe hypertension (systolic BP [SBP], 185 +/- 3.9 mmHg), proteinuria, afferent and efferent vasoconstriction, and glomerular hypertension. Rats that received AngII+MMF showed similar responses to AngII; however, they developed lower proteinuria (P < 0.05). At 2 wk, AngII was withdrawn and SBP returned toward normal. Rats were then placed on an HSD (4% NaCl), resulting in a progressive increase in SBP (155 +/- 8.2 mmHg at week 1 and 163 +/- 4.5 mmHg at week 5). GFR dynamic alterations persisted after AngII was stopped, i.e., afferent and efferent vasoconstriction, decreased glomerular plasma flow and single-nephron GFR, and lower ultrafiltration coefficient. These changes correlated with the thickening of the afferent arteriole and with focal tubulointerstitial injury. In the AngII+MMF group, SBP remained unchanged throughout the HSD period (146 +/- 2.3 mmHg at week 1 and 148 +/- 4.4 mmHg at week 5) in association with less afferent arteriolar thickening and tubulointerstitial injury. Single-nephron GFR, glomerular plasma flow, efferent resistance, and ultrafiltration coefficient returned to normal with a significant reduction in afferent resistance. These results suggest a critical role of cortical vasoconstriction in salt-sensitive hypertension. The MMF-induced prevention of these changes suggests that immune mechanisms are involved in the vasoconstrictive response.
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología, Mexico City, Mexico.
authors.forename: Martha
authors.initials: M
authors.lastname: Franco
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología, Mexico City, Mexico.
authors.forename: Edilia
authors.initials: E
authors.lastname: Tapia
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología, Mexico City, Mexico.
authors.forename: José
authors.initials: J
authors.lastname: Santamaría
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología, Mexico City, Mexico.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Zafra
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología, Mexico City, Mexico.
authors.forename: Romeo
authors.initials: R
authors.lastname: García-Torres
authors.affiliation: Division of Nephrology, University of Washington Medical Center, Seattle, Washington.
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Gordon
authors.affiliation: Division of Nephrology, University of Washington Medical Center, Seattle, Washington.
authors.forename: Héctor
authors.initials: H
authors.lastname: Pons
authors.affiliation: Instituto de Investigaciones Biomédicas, Maracaibo, Venezuela.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Rodríguez-Iturbe
authors.affiliation: Division of Nephrology, University of Washington Medical Center, Seattle, Washington.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Johnson
authors.affiliation: Department of Nephrology, Instituto Nacional de Cardiología, Mexico City, Mexico.
authors.forename: Jaime
authors.initials: J
authors.lastname: Herrera-Acosta
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D004357:Drug Synergism; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced* / Q000209:etiology* / Q000473:pathology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000473:pathology; D007672:Kidney Cortex / Q000098:blood supply*; D007678:Kidney Glomerulus / Q000098:blood supply; D008297:Male; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D007166:Immunosuppressive Agents; D000804:Angiotensin II; D012965:Sodium Chloride; D009173:Mycophenolic Acid