Tags

Type your tag names separated by a space and hit enter

Effects of AT1 receptor blockade on renal injury and mitogen-activated protein activity in Dahl salt-sensitive rats.
Kidney Int. 2004 Mar; 65(3):972-81.KI

Abstract

BACKGROUND

The mitogen-activated protein kinase (MAPK) cascade is an important intracellular mediator of angiotensin II (Ang II)-induced cell growth and differentiation. Here, we examined the effect of angiotensin II type 1 receptor (AT1) receptor blockade on renal injury and MAPK activity in Dahl salt-sensitive (DS) rats.

METHODS

DS rats were maintained on a high (H: 8.0%NaCl, N= 8) or low (L: 0.3%NaCl, N= 7) salt diet, or H + candesartan cilexetil (10 to 15 mg/kg/day, N= 8). Urinary protein excretion (UproteinV), renal cortical collagen content, and glomerular injury (assessed by semiquantitative morphometric analysis) were determined after 4-week treatments. Plasma and kidney Ang II levels were measured by radioimmunoassay. Protein levels of AT1 and AT2 receptors in the renal cortical tissues were analyzed by Western-blotting analyses. MAPKs activities, including extracellular signal-regulated kinases (ERK)1/2, c-Jun NH2-terminal kinases (JNK), p38 MAPK, and Big-MAPK-1 (BMK1), were measured by Western-blotting analyses or in vitro kinase assays.

RESULTS

DS/H rats showed higher mean blood pressure (MBP), UproteinV, and renal cortical collagen content than DS/L rats. Increased ERK1/2, JNK, and BMK1 activities were observed in renal cortical tissues of DS/H rats (approximately 6.3-, 4.5-, and 2.5-fold, respectively), whereas p38 MAPK activity was unchanged. Plasma Ang II levels were significantly reduced in DS/H rats compared with DS/L rats, whereas kidney Ang II contents and AT1 receptor protein levels were similar. Candesartan did not alter MBP, but significantly reduced UproteinV and collagen content, and ameliorated progressive sclerotic and proliferative glomerular changes. Furthermore, candesartan decreased renal tissue Ang II contents (from 216 +/- 19 to 46 +/- 3 fmol/mL) and ERK1/2, JNK, and BMK1 activities (-45%, -60%, and -70%, respectively) in DS/H rats.

CONCLUSION

In DS hypertensive rats, some of the renoprotective effects of AT1 receptor blockade are accompanied by reductions in intrarenal Ang II contents and MAPK activity, which might not be mediated through arterial pressure changes.

Authors+Show Affiliations

Department of Pharmacology, Research Equipment Center, Kagawa Medical University, Kagawa, Japan. akira@kms.ac.jpNo 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 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

14871417

Citation

Nishiyama, Akira, et al. "Effects of AT1 Receptor Blockade On Renal Injury and Mitogen-activated Protein Activity in Dahl Salt-sensitive Rats." Kidney International, vol. 65, no. 3, 2004, pp. 972-81.
Nishiyama A, Yoshizumi M, Rahman M, et al. Effects of AT1 receptor blockade on renal injury and mitogen-activated protein activity in Dahl salt-sensitive rats. Kidney Int. 2004;65(3):972-81.
Nishiyama, A., Yoshizumi, M., Rahman, M., Kobori, H., Seth, D. M., Miyatake, A., Zhang, G. X., Yao, L., Hitomi, H., Shokoji, T., Kiyomoto, H., Kimura, S., Tamaki, T., Kohno, M., & Abe, Y. (2004). Effects of AT1 receptor blockade on renal injury and mitogen-activated protein activity in Dahl salt-sensitive rats. Kidney International, 65(3), 972-81.
Nishiyama A, et al. Effects of AT1 Receptor Blockade On Renal Injury and Mitogen-activated Protein Activity in Dahl Salt-sensitive Rats. Kidney Int. 2004;65(3):972-81. PubMed PMID: 14871417.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of AT1 receptor blockade on renal injury and mitogen-activated protein activity in Dahl salt-sensitive rats. AU - Nishiyama,Akira, AU - Yoshizumi,Masanori, AU - Rahman,Matlubur, AU - Kobori,Hiroyuki, AU - Seth,Dale M, AU - Miyatake,Akira, AU - Zhang,Guo-Xing, AU - Yao,Li, AU - Hitomi,Hirofumi, AU - Shokoji,Takatomi, AU - Kiyomoto,Hideyasu, AU - Kimura,Shoji, AU - Tamaki,Toshiaki, AU - Kohno,Masakazu, AU - Abe,Youichi, PY - 2004/2/12/pubmed PY - 2004/10/9/medline PY - 2004/2/12/entrez SP - 972 EP - 81 JF - Kidney international JO - Kidney Int. VL - 65 IS - 3 N2 - BACKGROUND: The mitogen-activated protein kinase (MAPK) cascade is an important intracellular mediator of angiotensin II (Ang II)-induced cell growth and differentiation. Here, we examined the effect of angiotensin II type 1 receptor (AT1) receptor blockade on renal injury and MAPK activity in Dahl salt-sensitive (DS) rats. METHODS: DS rats were maintained on a high (H: 8.0%NaCl, N= 8) or low (L: 0.3%NaCl, N= 7) salt diet, or H + candesartan cilexetil (10 to 15 mg/kg/day, N= 8). Urinary protein excretion (UproteinV), renal cortical collagen content, and glomerular injury (assessed by semiquantitative morphometric analysis) were determined after 4-week treatments. Plasma and kidney Ang II levels were measured by radioimmunoassay. Protein levels of AT1 and AT2 receptors in the renal cortical tissues were analyzed by Western-blotting analyses. MAPKs activities, including extracellular signal-regulated kinases (ERK)1/2, c-Jun NH2-terminal kinases (JNK), p38 MAPK, and Big-MAPK-1 (BMK1), were measured by Western-blotting analyses or in vitro kinase assays. RESULTS: DS/H rats showed higher mean blood pressure (MBP), UproteinV, and renal cortical collagen content than DS/L rats. Increased ERK1/2, JNK, and BMK1 activities were observed in renal cortical tissues of DS/H rats (approximately 6.3-, 4.5-, and 2.5-fold, respectively), whereas p38 MAPK activity was unchanged. Plasma Ang II levels were significantly reduced in DS/H rats compared with DS/L rats, whereas kidney Ang II contents and AT1 receptor protein levels were similar. Candesartan did not alter MBP, but significantly reduced UproteinV and collagen content, and ameliorated progressive sclerotic and proliferative glomerular changes. Furthermore, candesartan decreased renal tissue Ang II contents (from 216 +/- 19 to 46 +/- 3 fmol/mL) and ERK1/2, JNK, and BMK1 activities (-45%, -60%, and -70%, respectively) in DS/H rats. CONCLUSION: In DS hypertensive rats, some of the renoprotective effects of AT1 receptor blockade are accompanied by reductions in intrarenal Ang II contents and MAPK activity, which might not be mediated through arterial pressure changes. SN - 0085-2538 UR - https://www.unboundmedicine.com/medline/citation/14871417/Effects_of_AT1_receptor_blockade_on_renal_injury_and_mitogen_activated_protein_activity_in_Dahl_salt_sensitive_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0085-2538(15)49790-X DB - PRIME DP - Unbound Medicine ER -