A potential role for the endothelin ET
A
receptor in salt-sensitive hypertension of the proANP gene-disrupted mouse |
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Authors: | P F O’Tierney E Angelis M Y Tse J J Pang M A Adams S C Pang |
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Institution: | (1) Department of Anatomy and Cell Biology, Queen’s University, Kingston, Ontario, Canada;(2) Department of Pharmacology and Toxicology, Queen’s University, Kingston, Ontario, Canada;(3) Department of Anatomy and Cell Biology, Queen’s University, Room 850 Botterell Hall, Kingston, Ontario, Canada, K7L 3N6 |
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Abstract: | 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. |
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Keywords: | salt-sensitive hypertension kidney endothelin-1 cGMP atrial natriuretic peptide |
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