In:
American Journal of Physiology-Renal Physiology, American Physiological Society, Vol. 303, No. 5 ( 2012-09-01), p. F659-F666
Abstract:
We have recently demonstrated that chronic infusion of exogenous ANG II, which induces blood pressure elevation, attenuates renal medullary endothelin B (ET B ) receptor function in rats. Moreover, this was associated with a reduction of ET B receptor expression in the renal inner medulla. The aim of this present work was to investigate the effect of a physiological increase in endogenous ANG II (low-salt diet) on the renal ET system, including ET B receptor function. We hypothesized that endogenous ANG II reduces renal medullary ET B receptor function during low-salt intake. Rats were placed on a low-salt diet (0.01–0.02% NaCl) for 2 wk to allow an increase in endogenous ANG II. In rats on normal-salt chow, the stimulation of renal medullary ET B receptor by ET B receptor agonist sarafotoxin 6c (S6c) causes an increase in water (3.6 ± 0.4 from baseline vs. 10.5 ± 1.3 μl/min following S6c infusion; P 〈 0.05) and sodium excretion (0.38 ± 0.06 vs. 1.23 ± 0.17 μmol/min; P 〈 0.05). The low-salt diet reduced the ET B -dependent diuresis (4.5 ± 0.5 vs. 6.1 ± 0.9 μl/min) and natriuresis (0.40 ± 0.11 vs. 0.46 ± 0.12 μmol/min) in response to acute intramedullary infusion of S6c. Chronic treatment with candesartan restored renal medullary ET B receptor function; urine flow was 7.1 ± 0.9 vs. 15.9 ± 1.7 μl/min ( P 〈 0.05), and sodium excretion was 0.4 ± 0.1 vs. 1.1 ± 0.1 μmol/min ( P 〈 0.05) before and after intramedullary S6c infusion, respectively. Receptor binding assays determined that the sodium-depleted diet resulted in a similar level of ET B receptor binding in renal inner medulla compared with rats on a normal-salt diet. Candesartan reduced renal inner medullary ET B receptor binding (1,414 ± 95 vs. 862 ± 50 fmol/mg; P 〈 0.05). We conclude that endogenous ANG II attenuates renal medullary ET B receptor function to conserve sodium during salt deprivation independently of receptor expression.
Type of Medium:
Online Resource
ISSN:
1931-857X
,
1522-1466
DOI:
10.1152/ajprenal.00213.2012
Language:
English
Publisher:
American Physiological Society
Publication Date:
2012
detail.hit.zdb_id:
1477287-5
