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Mineralocorticoid receptor blockade and calcium channel blockade have different renoprotective effects on glomerular and interstitial injury in rats.
Am J Physiol Renal Physiol. 2009 Sep; 297(3):F802-8.AJ

Abstract

We hypothesized that combination treatment with the mineralocorticoid receptor antagonist eplerenone and the calcium channel blocker amlodipine elicits better renoprotective effects than monotherapy with either drug, via different mechanisms in Dahl salt-sensitive (DS) hypertensive rats. DS rats were fed a high-salt diet (4% NaCl) for 10 wk and were treated with vehicle (n = 12), eplerenone (50 mg x kg(-1) x day(-1), p.o., n = 12), amlodipine (3 mg x kg(-1) x day(-1), p.o., n = 12), or eplerenone plus amlodipine (n = 12) after 2 wk of salt feeding. Vehicle-treated DS rats developed proteinuria, which was attenuated by eplerenone or amlodipine. Interestingly, eplerenone attenuated the glomerulosclerosis and podocyte injury, but amlodipine did not. Conversely, treatment with amlodipine markedly improved interstitial fibrosis, while the effect of eplerenone was minimal. Combination treatment markedly improved proteinuria, glomerulosclerosis, podocyte injury, and interstitial fibrosis in DS rats. Renal hypoxia estimated by pimonidazole, vascular endothelial growth factor expression, and density of peritubular endothelial cells was exacerbated by salt feeding. Amlodipine, either as monotherapy or in combination, ameliorated the renal hypoxia, whereas eplerenone treatment had no effect. In conclusion, both eplerenone and amlodipine attenuated renal injuries in high salt-fed DS rats, but the targets for renoprotection differed between these two drugs, with eplerenone predominantly acting on glomeruli and amlodipine acting on interstitium. The combination of eplerenone and amlodipine improved renal injury more effectively than either monotherapy in high salt-fed DS rats, presumably by achieving their own renoprotective effects.

Authors+Show Affiliations

Department of Pharmacology, Kagawa University Medical School, Kagawa, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

19535572

Citation

Du, Jun, et al. "Mineralocorticoid Receptor Blockade and Calcium Channel Blockade Have Different Renoprotective Effects On Glomerular and Interstitial Injury in Rats." American Journal of Physiology. Renal Physiology, vol. 297, no. 3, 2009, pp. F802-8.
Du J, Fan YY, Hitomi H, et al. Mineralocorticoid receptor blockade and calcium channel blockade have different renoprotective effects on glomerular and interstitial injury in rats. Am J Physiol Renal Physiol. 2009;297(3):F802-8.
Du, J., Fan, Y. Y., Hitomi, H., Kiyomoto, H., Kimura, S., Kong, C. Z., Noma, T., Kohno, M., Nishiyama, A., & Nakano, D. (2009). Mineralocorticoid receptor blockade and calcium channel blockade have different renoprotective effects on glomerular and interstitial injury in rats. American Journal of Physiology. Renal Physiology, 297(3), F802-8. https://doi.org/10.1152/ajprenal.00197.2009
Du J, et al. Mineralocorticoid Receptor Blockade and Calcium Channel Blockade Have Different Renoprotective Effects On Glomerular and Interstitial Injury in Rats. Am J Physiol Renal Physiol. 2009;297(3):F802-8. PubMed PMID: 19535572.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mineralocorticoid receptor blockade and calcium channel blockade have different renoprotective effects on glomerular and interstitial injury in rats. AU - Du,Jun, AU - Fan,Yu-Yan, AU - Hitomi,Hirofumi, AU - Kiyomoto,Hideyasu, AU - Kimura,Shoji, AU - Kong,Chui-Ze, AU - Noma,Takahisa, AU - Kohno,Masakazu, AU - Nishiyama,Akira, AU - Nakano,Daisuke, Y1 - 2009/06/17/ PY - 2009/6/19/entrez PY - 2009/6/19/pubmed PY - 2009/9/9/medline SP - F802 EP - 8 JF - American journal of physiology. Renal physiology JO - Am. J. Physiol. Renal Physiol. VL - 297 IS - 3 N2 - We hypothesized that combination treatment with the mineralocorticoid receptor antagonist eplerenone and the calcium channel blocker amlodipine elicits better renoprotective effects than monotherapy with either drug, via different mechanisms in Dahl salt-sensitive (DS) hypertensive rats. DS rats were fed a high-salt diet (4% NaCl) for 10 wk and were treated with vehicle (n = 12), eplerenone (50 mg x kg(-1) x day(-1), p.o., n = 12), amlodipine (3 mg x kg(-1) x day(-1), p.o., n = 12), or eplerenone plus amlodipine (n = 12) after 2 wk of salt feeding. Vehicle-treated DS rats developed proteinuria, which was attenuated by eplerenone or amlodipine. Interestingly, eplerenone attenuated the glomerulosclerosis and podocyte injury, but amlodipine did not. Conversely, treatment with amlodipine markedly improved interstitial fibrosis, while the effect of eplerenone was minimal. Combination treatment markedly improved proteinuria, glomerulosclerosis, podocyte injury, and interstitial fibrosis in DS rats. Renal hypoxia estimated by pimonidazole, vascular endothelial growth factor expression, and density of peritubular endothelial cells was exacerbated by salt feeding. Amlodipine, either as monotherapy or in combination, ameliorated the renal hypoxia, whereas eplerenone treatment had no effect. In conclusion, both eplerenone and amlodipine attenuated renal injuries in high salt-fed DS rats, but the targets for renoprotection differed between these two drugs, with eplerenone predominantly acting on glomeruli and amlodipine acting on interstitium. The combination of eplerenone and amlodipine improved renal injury more effectively than either monotherapy in high salt-fed DS rats, presumably by achieving their own renoprotective effects. SN - 1522-1466 UR - https://www.unboundmedicine.com/medline/citation/19535572/Mineralocorticoid_receptor_blockade_and_calcium_channel_blockade_have_different_renoprotective_effects_on_glomerular_and_interstitial_injury_in_rats_ L2 - http://www.physiology.org/doi/full/10.1152/ajprenal.00197.2009?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -