title: Tumor necrosis factor-alpha-angiotensin interactions and regulation of blood pressure.
abstract: OBJECTIVE
  To compare the levels of tumor necrosis factor-alpha (TNF) produced by medullary thick ascending limb tubules (MTAL) obtained from normotensive and angiotensin II (Ang II)-dependent hypertensive rats and determine whether TNF participates in a mechanism that opposes elevation of blood pressure by Ang II.
  
  
  METHODS
  We have previously demonstrated that in-vitro administration of Ang II increases production of TNF and prostaglandin E2 (PGE2) by the MTAL. We hypothesize that production of TNF and PGE2 by the MTAL is elevated in in-vivo models of Ang II-dependent hypertension and acts to modulate the pressor effects of Ang II. Thus, inhibition of TNF should disclose whether this cytokine acts to modulate Ang II-induced hypertension.
  
  
  METHODS
  MTAL tubules obtained from normotensive and Ang II-dependent hypertensive rats were isolated by enzymatic digestion and sieving. Tubules were cultured in the absence of exogenous Ang II. TNF and PGE2 levels were measured by enzyme-linked immunosorbent assay. Anti-TNF antiserum was administered intravenously to normotensive and Ang II-dependent hypertensive rats and their mean arterial pressures were measured.
  
  
  RESULTS
  Production of TNF and PGE2 was significantly greater in MTAL tubules isolated from Ang II hypertensive rats than it was in those from normotensive controls. Administration of anti-TNF antiserum exacerbated the Ang II-mediated increase in mean arterial pressure.
  
  
  CONCLUSIONS
  The higher levels of production of TNF and PGE2 by MTAL tubules isolated from Ang II hypertensive rats compared with those of normotensive controls are consistent with results of in-vitro experiments showing that administration of Ang II increases production of TNF and PGE2 by the MTAL. TNF and PGE2 participate in a counter-regulatory mechanism that opposes the pressor actions of Ang II.
authors.affiliation: Department of Pharmacology, New York Medical College, Valhalla 10595, USA.
authors.forename: N R
authors.initials: NR
authors.lastname: Ferreri
authors.forename: Y
authors.initials: Y
authors.lastname: Zhao
authors.forename: H
authors.initials: H
authors.lastname: Takizawa
authors.forename: J C
authors.initials: JC
authors.lastname: McGiff
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology* / Q000502:physiology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology*; D015232:Dinoprostone / Q000096:biosynthesis; D004347:Drug Interactions; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology; D007106:Immune Sera / Q000276:immunology / Q000494:pharmacology; D066298:In Vitro Techniques; D007679:Kidney Medulla; D008138:Loop of Henle / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology*
chemical_list: D007106:Immune Sera; D014409:Tumor Necrosis Factor-alpha; D000804:Angiotensin II; D015232:Dinoprostone