title: Novel mechanism of intra‑renal angiotensin II-induced sodium/proton exchanger 3 expression by losartan in spontaneously hypertensive rats.
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.
authors.affiliation: Institution of Life and Health Engineering, Jinan University, Guangzhou, Guangdong 510632, P.R. China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Laboratory, The Border Armed Police Central Hospital of Guangdong Province, Shenzhen, Guangdong 518023, P.R. China.
authors.forename: Kaishan
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Rehabilitation, The First People's Hospital of Foshan, Foshan, Guangdong 528000, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cui
authors.affiliation: Department of Physiology, Zunyi Medical College, Zhuhai Campus, Zhuhai, Guangdong 519041, P.R. China.
authors.forename: Jiongmei
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Physiology, Nanyang Medical College, Nanyang, Henan 473000, P.R. China.
authors.forename: Weina
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Physiology, Zunyi Medical College, Zhuhai Campus, Zhuhai, Guangdong 519041, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D015870:Gene Expression; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D000804:Angiotensin II; D000959:Antihypertensive Agents; D017874:Immediate-Early Proteins; D019808:Losartan; D017346:Protein Serine-Threonine Kinases; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D000099184:Serum-Glucocorticoid Regulated Kinases; C000613387:Slc9a3 protein, rat