title: Hemopexin activity is associated with angiotensin II responsiveness in humans.
abstract: BACKGROUND
  Hemopexin, an acute phase protein, can downregulate the angiotensin (ang) II type 1 receptor (AT1-R) in vitro. Whether hemopexin is involved in the responsiveness to ang II in vivo is unknown. Therefore, we tested whether variations in endogenous hemopexin activity are associated with the responsiveness of blood pressure to ang II in healthy volunteers.
  
  
  METHODS
  Healthy men (n = 33, age 26 ± 9) were studied in balance on low sodium (50 mmol Na per 24 h) and high sodium (200 mmol Na per 24 h) diet, respectively. After baseline measurements of blood pressure, ang II was infused at 0.3, 1 and 3 ng/kg per min for 1 h per dose. Hemopexin activity was measured at baseline in EDTA-plasma samples by an amidolytic assay with a chromogenic substrate suitable for hemopexin activity evaluation.
  
  
  RESULTS
  During high sodium the hemopexin activity was lower; 1.6 × 10 (0.6 × 10 - 4.7 × 10) versus 2.8 × 10 (1.1 × 10 - 5.1 × 10) arbitrary units (P < 0.01) and the pressor response to 3 ng ang II/kg per minute larger than during low sodium (17.6 ± 6.5 versus 14.6 ± 6.9 mmHg, P < 0.01). Hemopexin activity negatively correlated with the pressor response to ang II during either type of sodium intake (high sodium: r = 0.42, P < 0.05; low sodium: r = 0.35, P < 0.05).
  
  
  CONCLUSIONS
  These in-vivo data obtained in healthy individuals support recent in-vitro data showing that active hemopexin downregulates the availability of the AT1-R. Therefore, activated hemopexin might be considered as a factor mediating ang II effects upon blood pressure by modulating AT1-R availability.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Jan A
authors.initials: JA
authors.lastname: Krikken
authors.forename: Anna T
authors.initials: AT
authors.lastname: Lely
authors.forename: Stephan J L
authors.initials: SJ
authors.lastname: Bakker
authors.forename: Theo
authors.initials: T
authors.lastname: Borghuis
authors.forename: Marijke M
authors.initials: MM
authors.lastname: Faas
authors.forename: Harry
authors.initials: H
authors.lastname: van Goor
authors.forename: Gerjan
authors.initials: G
authors.lastname: Navis
authors.forename: Winston W
authors.initials: WW
authors.lastname: Bakker
mesh_terms: D000293:Adolescent; D000328:Adult; D000804:Angiotensin II / Q000502:physiology*; D006466:Hemopexin / Q000502:physiology*; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D000804:Angiotensin II; D006466:Hemopexin