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Effect of mineralocorticoid receptor blockade on the renal renin-angiotensin system in Dahl salt-sensitive hypertensive rats.
J Hypertens. 2009 Apr; 27(4):800-5.JH

Abstract

BACKGROUND

The (pro)renin receptor exists in the kidney, blood vessels and the heart. (Pro)renin binds to the receptor and induces tissue injuries directly, completely independent of angiotensin II (Ang II). The renal renin-angiotensin-aldosterone system is activated in salt-sensitive hypertensive rats with in-vitro studies showing aldosterone increases angiotensin-converting enzyme (ACE) activity, renin production and angiotensin II type 1 receptor (AT1R) activity. However, the effect of blockade of mineralocorticoid receptor on the renal (pro)renin receptor, angiotensinogen, ACE and AT1R in Dahl salt-sensitive rats is unknown.

METHODS

The following parameters were measured in Dahl salt-sensitive rats and in Dahl salt-resistant rats fed high-salt or low-salt diets and treated for 8 weeks with or without eplerenone (100 mg/kg per day, orally): blood pressure, plasma renin activity, plasma aldosterone concentration, kidney weight and Ang II contents, urinary protein excretion, glomerular injury (assessed by semiquantitative morphometric analysis) and levels of expression in the kidney of (pro)renin receptor protein and messenger RNA (mRNA) for angiotensinogen, ACE and AT1R.

RESULTS

Dahl salt-sensitive rats fed a high-salt diet had increased kidney/body weight (175%) and urinary protein excretion (886%) and decreased plasma renin activity and plasma aldosterone concentration. The rats developed progressive sclerotic and proliferative glomerular changes, concomitant with increased expression of renal (pro)renin receptor protein and mRNA levels of angiotensinogen, ACE and AT1R and kidney Ang II content. Treatment with eplerenone in Dahl salt-sensitive rats was associated with significant improvements in kidney to body weight ratio, urinary protein excretion and renal injury scores and decreased renal (pro)renin receptor protein expression and angiotensinogen and AT1R mRNA levels and kidney Ang II content.

CONCLUSION

A high salt diet increased the renal renin-angiotensin system, whereas blockade of mineralocorticoid receptors attenuated renal injuries by decreasing the activity of tissue renin-angiotensin system in Dahl salt-sensitive rats.

Authors+Show Affiliations

Department of Internal Medicine, Graduate School of Medical Science, Kanazawa University, Kanazawa, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19516179

Citation

Zhu, Aoshuang, et al. "Effect of Mineralocorticoid Receptor Blockade On the Renal Renin-angiotensin System in Dahl Salt-sensitive Hypertensive Rats." Journal of Hypertension, vol. 27, no. 4, 2009, pp. 800-5.
Zhu A, Yoneda T, Demura M, et al. Effect of mineralocorticoid receptor blockade on the renal renin-angiotensin system in Dahl salt-sensitive hypertensive rats. J Hypertens. 2009;27(4):800-5.
Zhu, A., Yoneda, T., Demura, M., Karashima, S., Usukura, M., Yamagishi, M., & Takeda, Y. (2009). Effect of mineralocorticoid receptor blockade on the renal renin-angiotensin system in Dahl salt-sensitive hypertensive rats. Journal of Hypertension, 27(4), 800-5. https://doi.org/10.1097/HJH.0b013e328325d861
Zhu A, et al. Effect of Mineralocorticoid Receptor Blockade On the Renal Renin-angiotensin System in Dahl Salt-sensitive Hypertensive Rats. J Hypertens. 2009;27(4):800-5. PubMed PMID: 19516179.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of mineralocorticoid receptor blockade on the renal renin-angiotensin system in Dahl salt-sensitive hypertensive rats. AU - Zhu,Aoshuang, AU - Yoneda,Takashi, AU - Demura,Masashi, AU - Karashima,Shigehiro, AU - Usukura,Mikiya, AU - Yamagishi,Masakazu, AU - Takeda,Yoshiyu, PY - 2009/6/12/entrez PY - 2009/6/12/pubmed PY - 2009/8/27/medline SP - 800 EP - 5 JF - Journal of hypertension JO - J. Hypertens. VL - 27 IS - 4 N2 - BACKGROUND: The (pro)renin receptor exists in the kidney, blood vessels and the heart. (Pro)renin binds to the receptor and induces tissue injuries directly, completely independent of angiotensin II (Ang II). The renal renin-angiotensin-aldosterone system is activated in salt-sensitive hypertensive rats with in-vitro studies showing aldosterone increases angiotensin-converting enzyme (ACE) activity, renin production and angiotensin II type 1 receptor (AT1R) activity. However, the effect of blockade of mineralocorticoid receptor on the renal (pro)renin receptor, angiotensinogen, ACE and AT1R in Dahl salt-sensitive rats is unknown. METHODS: The following parameters were measured in Dahl salt-sensitive rats and in Dahl salt-resistant rats fed high-salt or low-salt diets and treated for 8 weeks with or without eplerenone (100 mg/kg per day, orally): blood pressure, plasma renin activity, plasma aldosterone concentration, kidney weight and Ang II contents, urinary protein excretion, glomerular injury (assessed by semiquantitative morphometric analysis) and levels of expression in the kidney of (pro)renin receptor protein and messenger RNA (mRNA) for angiotensinogen, ACE and AT1R. RESULTS: Dahl salt-sensitive rats fed a high-salt diet had increased kidney/body weight (175%) and urinary protein excretion (886%) and decreased plasma renin activity and plasma aldosterone concentration. The rats developed progressive sclerotic and proliferative glomerular changes, concomitant with increased expression of renal (pro)renin receptor protein and mRNA levels of angiotensinogen, ACE and AT1R and kidney Ang II content. Treatment with eplerenone in Dahl salt-sensitive rats was associated with significant improvements in kidney to body weight ratio, urinary protein excretion and renal injury scores and decreased renal (pro)renin receptor protein expression and angiotensinogen and AT1R mRNA levels and kidney Ang II content. CONCLUSION: A high salt diet increased the renal renin-angiotensin system, whereas blockade of mineralocorticoid receptors attenuated renal injuries by decreasing the activity of tissue renin-angiotensin system in Dahl salt-sensitive rats. SN - 1473-5598 UR - https://www.unboundmedicine.com/medline/citation/19516179/Effect_of_mineralocorticoid_receptor_blockade_on_the_renal_renin_angiotensin_system_in_Dahl_salt_sensitive_hypertensive_rats_ L2 - http://dx.doi.org/10.1097/HJH.0b013e328325d861 DB - PRIME DP - Unbound Medicine ER -