Novel mechanism of intra‑renal angiotensin II-induced sodium/proton exchanger 3 expression by losartan in spontaneously hypertensive rats

Fan,Xiaoqin; Liu,Kaishan; Cui,Wei; Huang,Jiongmei; Wang,Weina; Gao,Yuan

doi:10.3892/mmr.2014.2492

November-2014 Volume 10 Issue 5

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

November-2014 Volume 10 Issue 5

Full Size Image

Article

Novel mechanism of intra‑renal angiotensin II-induced sodium/proton exchanger 3 expression by losartan in spontaneously hypertensive rats

Authors:
- Xiaoqin Fan
- Kaishan Liu
- Wei Cui
- Jiongmei Huang
- Weina Wang
- Yuan Gao
View Affiliations / Copyright

Affiliations: Institution of Life and Health Engineering, Jinan University, Guangzhou, Guangdong 510632, P.R. China, Department of Laboratory, The Border Armed Police Central Hospital of Guangdong Province, Shenzhen, Guangdong 518023, P.R. China, Department of Rehabilitation, The First People's Hospital of Foshan, Foshan, Guangdong 528000, P.R. China, Department of Physiology, Zunyi Medical College, Zhuhai Campus, Zhuhai, Guangdong 519041, P.R. China, Department of Physiology, Nanyang Medical College, Nanyang, Henan 473000, P.R. China
Pages: 2483-2488
|
Published online on: August 14, 2014

https://doi.org/10.3892/mmr.2014.2492
Expand metrics +

Abstract

The present study aimed to investigate the molecular pharmacodynamic mechanisms of losartan used in the treatment of hypertension. A total of 12 spontaneously hypertensive rats (SHR) were divided randomly into an SHR group treated with saline and LOS group treated with losartan. Six Wistar‑kyoto rats (WKY) were enrolled as the WKY group with saline in the study. The LOS group received 30 mg/kg/day losartan by intragastric injection, while the SHR and WKY were fed the same volume of saline. The dosage was modulated according to the weekly weight. Changes in blood pressure were measured by the indirect tail cuff method. Angiotensin (Ang) II production in the plasma and renal tissue was measured by an immunoradiometric method. Na+/H+ exchanger (NHE)3 and serum and glucocorticoid‑inducible kinase (SGK)1 were assessed by quantitative polymerase chain reaction (qPCR) and western blot analysis. When compared with the WKY group, the blood pressure of the SHR and LOS groups were higher prior to treatment with losartan. Following two weeks, blood pressure was reduced and the trend continued to decrease over the following six weeks. The plasma and renal tissue levels of Ang II in the SHR and LOS groups were significantly higher than those in the WKY group. NHE3 and SGK1 were increased at the mRNA and protein level in the SHR group, and losartan reduced the expression of both of them. The results suggested that in hypertensive rats, the circular and tissue renin angiotensin systems were activated, and the increased Ang II stimulated the expression of NHE3 and SGK1, which was reduced by losartan. Therefore, the effects of losartan in hypertension may be associated with the Ang II‑SGK1‑NHE3 of intra‑renal tissue.

View Figures

View References

1	Gu D, Reynolds K, Wu X, et al: Prevalence, awareness, treatment, and control of hypertension in China. Hypertension. 40:920–927. 2002. View Article : Google Scholar : PubMed/NCBI
2	Griendling KK, Murphy T and Alexander RW: Molecular biology of the renin-angiotensin system. Circulation. 87:1816–1828. 1993. View Article : Google Scholar
3	Peach MJ: Renin-angiotensin system: biochemistry and mechanisms of action. Physiol Rev. 57:313–370. 1977.PubMed/NCBI
4	Kobori H, Nangaku M, Navar LG and Nishiyama A: The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease. Pharmacol Rev. 59:251–287. 2007. View Article : Google Scholar : PubMed/NCBI
5	Paul M, Mehr AP and Kreutz R: Physiology of local renin-angiotensin systems. Physiological Reviews. 86:747–803. 2006. View Article : Google Scholar : PubMed/NCBI
6	Biemesderfer D, Pizzonia J, Abu-Alfa A, et al: NHE3: a Na⁺/H⁺ exchanger isoform of renal brush border. Am J Physiol. 265:F736–F742. 1993.PubMed/NCBI
7	Malo ME and Fliegel L: Physiological role and regulation of the Na⁺/H⁺ exchanger. Can J Physiol Pharmacol. 84:1081–1095. 2006. View Article : Google Scholar : PubMed/NCBI
8	Orlowski J and Grinstein S: Diversity of the mammalian sodium/proton exchanger SLC9 gene family. Pfluegers Archiv. 447:549–565. 2004. View Article : Google Scholar : PubMed/NCBI
9	Amemiya M, Loffing J, Lötscher M, et al: Expression of NHE-3 in the apical membrane of rat renal proximal tubule and thick ascending limb. Kidney Int. 48:1206–1215. 1995. View Article : Google Scholar : PubMed/NCBI
10	Khan I, Batinic-Haberle I and Benov LT: Effect of potent redox-modulating manganese porphyrin, MnTM-2-PyP, on the Na⁺/H⁺ exchangers NHE-1 and NHE-3 in the diabetic rat. Redox Rep. 14:236–242. 2009. View Article : Google Scholar : PubMed/NCBI
11	Pao AC: SGK regulation of renal sodium transport. Curr Opin Nephrol Hypertens. 21:534–540. 2012. View Article : Google Scholar : PubMed/NCBI
12	Lang F, Huang DY and Vallon V: SGK, renal function and hypertension. J Nephrol. 23(Suppl 16): S124–S129. 2010.PubMed/NCBI
13	Smith DH: Comparison of angiotensin II type 1 receptor antagonists in the treatment of essential hypertension. Drugs. 68:1207–1225. 2008. View Article : Google Scholar : PubMed/NCBI
14	Xu L, Dixit MP, Nullmeyer KD, et al: Regulation of Na⁺/H⁺ exchanger-NHE3 by angiotensin-II in OKP cells. Biochimica et Biochim Biophys Acta. 1758:519–526. 2006.
15	Moe OW: Acute regulation of proximal tubule apical membrane Na/H exchanger NHE-3: role of phosphorylation, protein trafficking, and regulatory factors. J Am Soc Nephrol. 10:2412–2425. 1999.PubMed/NCBI
16	Stevens VA, Saad S, Poronnik P, et al: The role of SGK-1 in angiotensin II-mediated sodium reabsorption in human proximal tubular cells. Nephrol Dial Transplant. 23:1834–1843. 2008. View Article : Google Scholar : PubMed/NCBI
17	Wang D, Sun H, Lang F and Yun CC: Activation of NHE3 by dexamethasone requires phosphorylation of NHE3 at Ser663 by SGK1. Am J Physiol Cell Physiol. 289:C802–C810. 2005. View Article : Google Scholar : PubMed/NCBI
18	Lu D, Raizada MK, Iyer S, et al: Losartan versus gene therapy chronic control of high blood pressure in spontaneously hypertensive rats. Hypertension. 30:363–370. 1997. View Article : Google Scholar : PubMed/NCBI
19	Baumann M, Janssen B, Rob Hermans J, et al: Renal medullary effects of transient prehypertensive treatment in young spontaneously hypertensive rats. Acta Physiologica (Oxf). 196:231–237. 2009. View Article : Google Scholar : PubMed/NCBI
20	Koprdova R, Cebova M and Kristek F: Long-term effect of losartan administration on blood pressure, heart and structure of coronary artery of young spontaneously hypertensive rats. Physiol Res. 58:327–325. 2009.PubMed/NCBI
21	Kaunisto KM and Rajaniemi HJ: Expression and localization of the Na⁺/H⁺ exchanger isoform NHE3 in the rat efferent ducts. J Androl. 23:237–241. 2002.PubMed/NCBI
22	Karim Z, Gérard B, Bakouh N, et al: NHERF1 mutations and responsiveness of renal parathyroid hormone. N Engl J Med. 359:1128–1135. 2008. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Novel mechanism of intra‑renal angiotensin II-induced sodium/proton exchanger 3 expression by losartan in spontaneously hypertensive rats

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Related Articles