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Mineralocorticoid receptor activation contributes to salt-induced hypertension and renal injury in prepubertal Dahl salt-sensitive rats.
Nephrol Dial Transplant. 2010 Sep; 25(9):2879-89.ND

Abstract

BACKGROUND

Excessive prepubertal salt intake permanently increases blood pressure (BP). We examined the role that the mineralocorticoid receptor (MR) plays in the salt-induced hypertension and renal damage of prepubertal Dahl salt-sensitive (SS) rats.

METHODS

Prepubertal (6 weeks old) and adult (10 weeks old) Dahl SS rats fed a high (8.0%) salt (HS) diet for 10 weeks were compared in terms of BP and renal function. The effect of treatment between the ages of 4 and 10 weeks with the MR antagonist eplerenone (0.125% in chow), the vasodilator hydralazine (50 mg/kg/day in drinking water) or the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (tempol) (0.6 mmol/kg/day in drinking water) on the BP and renal function of prepubertal rats fed a HS diet for 10 weeks was also examined.

RESULTS

Excessive salt intake starting in prepuberty was associated with a higher BP increase and greater proteinuria than if it started in adulthood. Eplerenone moderately reduced BP and markedly improved renal injury during its administration in prepubertal rats. These effects continued after drug discontinuation. Hydralazine greatly decreased BP and reduced proteinuria, but these effects were completely lost after drug discontinuation. Excessive salt increased urinary 8-hydroxy-2'-deoxyguanosine levels, intrarenal macrophage infiltration and renal plasminogen activator inhibitor-1 and transforming growth factor-beta mRNA expression. Eplerenone, but not hydralazine, attenuated these salt-induced inflammatory reactions. Tempol improved salt-induced hypertension and renal injury, even after its discontinuation.

CONCLUSIONS

Dahl SS rats exposed to excessive salt in prepubescence show a permanent increase in susceptibility to salt-induced hypertension and proteinuria. MR activation may promote these effects at least in part by inducing oxidation and inflammation.

Authors+Show Affiliations

Department of Nephrology and Endocrinology, University of Tokyo, School of Medicine, Tokyo, Japan. hirookawarazaki@yahoo.co.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20466668

Citation

Kawarazaki, Hiroo, et al. "Mineralocorticoid Receptor Activation Contributes to Salt-induced Hypertension and Renal Injury in Prepubertal Dahl Salt-sensitive Rats." Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, vol. 25, no. 9, 2010, pp. 2879-89.
Kawarazaki H, Ando K, Nagae A, et al. Mineralocorticoid receptor activation contributes to salt-induced hypertension and renal injury in prepubertal Dahl salt-sensitive rats. Nephrol Dial Transplant. 2010;25(9):2879-89.
Kawarazaki, H., Ando, K., Nagae, A., Fujita, M., Matsui, H., & Fujita, T. (2010). Mineralocorticoid receptor activation contributes to salt-induced hypertension and renal injury in prepubertal Dahl salt-sensitive rats. Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association, 25(9), 2879-89. https://doi.org/10.1093/ndt/gfq197
Kawarazaki H, et al. Mineralocorticoid Receptor Activation Contributes to Salt-induced Hypertension and Renal Injury in Prepubertal Dahl Salt-sensitive Rats. Nephrol Dial Transplant. 2010;25(9):2879-89. PubMed PMID: 20466668.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mineralocorticoid receptor activation contributes to salt-induced hypertension and renal injury in prepubertal Dahl salt-sensitive rats. AU - Kawarazaki,Hiroo, AU - Ando,Katsuyuki, AU - Nagae,Ai, AU - Fujita,Megumi, AU - Matsui,Hiromitsu, AU - Fujita,Toshiro, Y1 - 2010/04/20/ PY - 2010/5/15/entrez PY - 2010/5/15/pubmed PY - 2010/12/25/medline SP - 2879 EP - 89 JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association JO - Nephrol. Dial. Transplant. VL - 25 IS - 9 N2 - BACKGROUND: Excessive prepubertal salt intake permanently increases blood pressure (BP). We examined the role that the mineralocorticoid receptor (MR) plays in the salt-induced hypertension and renal damage of prepubertal Dahl salt-sensitive (SS) rats. METHODS: Prepubertal (6 weeks old) and adult (10 weeks old) Dahl SS rats fed a high (8.0%) salt (HS) diet for 10 weeks were compared in terms of BP and renal function. The effect of treatment between the ages of 4 and 10 weeks with the MR antagonist eplerenone (0.125% in chow), the vasodilator hydralazine (50 mg/kg/day in drinking water) or the superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl-piperidine-N-oxyl (tempol) (0.6 mmol/kg/day in drinking water) on the BP and renal function of prepubertal rats fed a HS diet for 10 weeks was also examined. RESULTS: Excessive salt intake starting in prepuberty was associated with a higher BP increase and greater proteinuria than if it started in adulthood. Eplerenone moderately reduced BP and markedly improved renal injury during its administration in prepubertal rats. These effects continued after drug discontinuation. Hydralazine greatly decreased BP and reduced proteinuria, but these effects were completely lost after drug discontinuation. Excessive salt increased urinary 8-hydroxy-2'-deoxyguanosine levels, intrarenal macrophage infiltration and renal plasminogen activator inhibitor-1 and transforming growth factor-beta mRNA expression. Eplerenone, but not hydralazine, attenuated these salt-induced inflammatory reactions. Tempol improved salt-induced hypertension and renal injury, even after its discontinuation. CONCLUSIONS: Dahl SS rats exposed to excessive salt in prepubescence show a permanent increase in susceptibility to salt-induced hypertension and proteinuria. MR activation may promote these effects at least in part by inducing oxidation and inflammation. SN - 1460-2385 UR - https://www.unboundmedicine.com/medline/citation/20466668/Mineralocorticoid_receptor_activation_contributes_to_salt_induced_hypertension_and_renal_injury_in_prepubertal_Dahl_salt_sensitive_rats_ L2 - https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfq197 DB - PRIME DP - Unbound Medicine ER -