Identification of salt-sensitive genes in the kidneys of Dahl rats.
OBJECTIVE
Inherited differences in renal function underlie the effect of high salt diets on blood pressure in Dahl rats. We probed the kidneys of inbred Dahl SS/Jr and SR/Jr for anonymous and candidate genes whose expression was regulated by dietary sodium.


METHODS
mRNA quantitation of both candidate genes implicated in sodium excretion and anonymous gene products found by differential hybridization in the kidneys of salt-resistant (SR) and salt sensitive (SS) inbred Dahl rats on high and low salt diets for 21 days.


RESULTS
Differential screening revealed a cDNA clone (H1) that showed increased dietary salt-dependent expression only in SS rats. Sequencing of the H1 cDNA showed it was the Dahl rat homologue to a perchloric acid soluble protein expressed in liver and kidney. Among candidate genes, transcript levels of arginosuccinate synthetase (AS) and arginosuccinate lyase (AL) were higher in SS on low salt diets, and AS mRNA increased in response to a high salt diet in SR. Renal mRNA for the ANP-A and the vasopressin type II receptors did not differ by strain or dietary conditions.


CONCLUSIONS
Three new salt-sensitive genes were detected in the kidneys of inbred Dahl rats. Two genes encode enzymes in the biosynthesis of L-arginine. The upregulation of these genes by dietary salt indicates increased demand and biosynthesis of L-arginine in Dahl SS rats. A third gene encodes a small acid-soluble protein thought to influence the transcription/translation of numerous genes. Further studies will be needed to determine the nature of the association of these genes with salt-sensitivity and blood pressure.
Lighthall
Geoffrey K
GK
Department of Physiology and Medicine, University of Maryland, Veterans Administration Medical Center, Baltimore, Maryland 21201, USA.
Hamilton
Bruce P
BP
Hamlyn
John M
JM
D000818:Animals; D001120:Arginine / Q000096:biosynthesis; D001123:Argininosuccinate Lyase / Q000235:genetics; D001124:Argininosuccinate Synthase / Q000235:genetics; D001794:Blood Pressure / Q000235:genetics; D015152:Blotting, Northern; D018076:DNA, Complementary; D005820:Genetic Testing; D006824:Hybridization, Genetic; D006973:Hypertension / Q000235:genetics*; D007668:Kidney / Q000502:physiology*; D008297:Male; D051381:Rats; D020303:Rats, Inbred Dahl / Q000235:genetics*; D017673:Sodium Chloride, Dietary / Q000494:pharmacology
D018076:DNA, Complementary; D017673:Sodium Chloride, Dietary; D001120:Arginine; D001123:Argininosuccinate Lyase; D001124:Argininosuccinate Synthase