A potential role for the endothelin ETA receptor in salt-sensitive hypertension of the proANP gene-disrupted mouse.
We have previously shown that the partial disruption of the gene for atrial natriuretic peptide (ANP) results in a salt-sensitive phenotype. The present study examined the possibility that alterations in either the ANP natriuretic pathway or endothelin (ET) system in the kidney of the salt-challenged ANP +/- mouse was responsible for its salt-sensitive phenotype. Plasma ANP levels and renal cGMP activity were increased in response to a salt load in both ANP +/+ and +/- mice. However, the mRNA expression of proANP was found to be increased only in the ANP +/- kidney along with its guanylyl cyclase-linked receptor, NPRA; the upregulation of NPRA mRNA was limited to the renal medulla. This suggests that the renal ANP pathway remains capable of responding to a salt load in the ANP +/- animal, but may be compensating for other dysfunctional pathways. We also report a significant increase in renal ET-1 mRNA and ETA receptor protein expression in medulla and cortex of the salt-treated, ANP +/- mouse, but not its wild-type counterpart. In fact, ETA expression decreased in the renal cortex of the ANP +/+ salt-treated animal. The ETB receptor expression was not affected by diet in either genotype. We hypothesize that the salt-sensitive hypertension in the ANP +/- mouse is exacerbated, and possibly driven by the vasoconstrictive effects resulting from an upregulated ET-1/ETA pathway.
O'Tierney
P F
PF
Department of Anatomy and Cell Biology, Queen's University, Kingston, Ontario, Canada.
Angelis
E
E
Tse
M Y
MY
Pang
J J
JJ
Adams
M A
MA
Pang
S C
SC
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000235:genetics* / Q000502:physiology*; D015153:Blotting, Western; D006152:Cyclic GMP / Q000032:analysis; D004195:Disease Models, Animal; D006162:Guanylate Cyclase / Q000502:physiology; D006579:Heterozygote; D006720:Homozygote; D006973:Hypertension / Q000235:genetics / Q000503:physiopathology*; D007668:Kidney / Q000737:chemistry / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000032:analysis; D044022:Receptor, Endothelin A / Q000502:physiology*; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D018000:Receptors, Peptide / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012982:Sodium, Dietary; D015854:Up-Regulation
D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D018000:Receptors, Peptide; D012982:Sodium, Dietary; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D000074261:Receptors, Enterotoxin; D050705:Receptors, Guanylate Cyclase-Coupled; D006152:Cyclic GMP