Regulation of type 1 angiotensin II receptor and its subtype gene expression in kidney by sodium loading and angiotensin II infusion.
OBJECTIVE
To test the hypothesis that a high salt intake decreases gene expression of both type 1 angiotensin receptor subtypes 1A and 1B (AT1A and AT1B) and diminishes AT1 receptor density in the kidney through an angiotensin II (Ang II)-independent mechanism.


METHODS
Wistar rats were divided into four groups and fed a normal-sodium diet (0.5%, NSD), NSD + 25 ng/kg per min Ang II infusion, a high-sodium diet (4%, HSD), or HSD + Ang II infusion for 2 weeks. Quantitative reverse transcriptase-polymerase chain reaction was used for analysis of changes in renal AT1A and AT1B messenger RNA (mRNA) levels. Radioligand binding assays were used for measurement of Ang II receptor density.


RESULTS
Body weight and mean arterial pressure did not differ among the four groups. Renal AT1A and AT1B mRNA levels were decreased significantly in NSD + Ang II and HSD + Ang II groups compared with those in the NSD group. Renal AT1B mRNA was also decreased significantly in HSD versus NSD. The renal AT1 receptor density was decreased significantly in NSD + Ang II and HSD + Ang II, but was not changed in HSD compared with NSD.


CONCLUSIONS
A high salt intake downregulates the AT1B mRNA expression but does not change the AT1A mRNA expression and AT1 receptor density in the kidney, suggesting that differential regulation occurs in the kidney. Infusion of a nonpressor dose of Ang II, either alone or in conjunction with a high salt intake, downregulates the AT1 receptor and its subtype gene expression in the kidney, suggesting that Ang II regulates these responses through a negative feedback mechanism.
Wang
D H
DH
Department of Internal Medicine, Hypertension and Vascular Research Laboratories, University of Texas Medical Branch, Galveston 77555, USA.
Du
Y
Y
Yao
A
A
Hu
Z
Z
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D005786:Gene Expression Regulation; D007668:Kidney / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D011945:Receptors, Angiotensin / Q000145:classification / Q000235:genetics*; D012982:Sodium, Dietary / Q000008:administration & dosage*
D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D012982:Sodium, Dietary; D000804:Angiotensin II