title: Interactive roles of NPR1 gene-dosage and salt diets on cardiac angiotensin II, aldosterone and pro-inflammatory cytokines levels in mutant mice.
abstract: OBJECTIVE
  The objective of the present study was to elucidate the interactive roles of guanylyl cyclase/natriuretic peptide receptor-A (NPRA) gene (Npr1) and salt diets on cardiac angiotensin II (ANG II), aldosterone and pro-inflammatory cytokines levels in Npr1 gene-targeted (1-copy, 2-copy, 3-copy, 4-copy) mice.
  
  
  METHODS
  Npr1 genotypes included 1-copy gene-disrupted heterozygous (+/-), 2-copy wild-type (+/+), 3-copy gene-duplicated heterozygous (++/+) and 4-copy gene-duplicated homozygous (++/++) mice. Animals were fed low, normal and high-salt diets. Plasma and cardiac levels of ANG II, aldosterone and pro-inflammatory cytokines were determined.
  
  
  RESULTS
  With a high-salt diet, cardiac ANG II levels were increased (+) in 1-copy mice (13.7 ± 2.8 fmol/mg protein, 111%) compared with 2-copy mice (6.5 ± 0.6), but decreased (-) in 4-copy (4.0 ± 0.5, 38%) mice. Cardiac aldosterone levels were increased (+) in 1-copy mice (80 ± 4 fmol/mg protein, 79%) compared with 2-copy mice (38 ± 3). Plasma tumour necrosis factor alpha was increased (+) in 1-copy mice (30.27 ± 2.32 pg/ml, 38%), compared with 2-copy mice (19.36 ± 2.49, 24%), but decreased (-) in 3-copy (11.59 ± 1.51, 12%) and 4-copy (7.13 ± 0.52, 22%) mice. Plasma interleukin (IL)-6 and IL-1α levels were also significantly increased (+) in 1-copy compared with 2-copy mice but decreased (-) in 3-copy and 4-copy mice.
  
  
  CONCLUSIONS
  These results demonstrate that a high-salt diet aggravates cardiac ANG II, aldosterone and pro-inflammatory cytokine levels in Npr1 gene-disrupted 1-copy mice, whereas, in Npr1 gene-duplicated (3-copy and 4-copy) mice, high salt did not render such elevation, suggesting the potential roles of Npr1 against salt loading.
authors.affiliation: Department of Physiology, Tulane University Health Sciences Center, School of Medicine, New Orleans, Louisiana, USA.
authors.forename: Di
authors.initials: D
authors.lastname: Zhao
authors.forename: Subhankar
authors.initials: S
authors.lastname: Das
authors.forename: Kailash N
authors.initials: KN
authors.lastname: Pandey
mesh_terms: D000450:Aldosterone / Q000097:blood / Q000378:metabolism*; D000804:Angiotensin II / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000235:genetics*; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D004032:Diet; D018628:Gene Dosage; D006321:Heart / Q000502:physiology*; D051379:Mice; D008817:Mice, Mutant Strains; D017461:Receptors, Atrial Natriuretic Factor / Q000235:genetics*; D012965:Sodium Chloride / Q000008:administration & dosage*
chemical_list: D016207:Cytokines; D000804:Angiotensin II; D012965:Sodium Chloride; D000450:Aldosterone; D017461:Receptors, Atrial Natriuretic Factor; C091715:atrial natriuretic factor receptor A