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Perinatally administered losartan augments renal ACE2 expression but not cardiac or renal Mas receptor in spontaneously hypertensive rats.
J Cell Mol Med. 2015 Aug; 19(8):1965-74.JC

Abstract

Since the identification of the alternative angiotensin converting enzyme (ACE)2/Ang-(1-7)/Mas receptor axis, renin-angiotensin system (RAS) is a new complex target for a pharmacological intervention. We investigated the expression of RAS components in the heart and kidney during the development of hypertension and its perinatal treatment with losartan in young spontaneously hypertensive rats (SHR). Expressions of RAS genes were studied by the RT-PCR in the left ventricle and kidney of rats: normotensive Wistar, untreated SHR, SHR treated with losartan since perinatal period until week 9 of age (20 mg/kg/day) and SHR treated with losartan only until week 4 of age and discontinued until week 9. In the hypertrophied left ventricle of SHR, cardiac expressions of Ace and Mas were decreased while those of AT1 receptor (Agtr1a) and Ace2 were unchanged. Continuous losartan administration reduced LV weight (0.43 ± 0.02; P < 0.05 versus SHR) but did not influence altered cardiac RAS expression. Increased blood pressure in SHR (149 ± 2 in SHR versus 109 ± 2 mmHg in Wistar; P < 0.05) was associated with a lower renal expressions of renin, Agtr1a and Mas and with an increase in ACE2. Continuous losartan administration lowered blood pressure to control levels (105 ± 3 mmHg; P < 0.05 versus SHR), however, only renal renin and ACE2 were significantly up-regulated (for both P < 0.05 versus SHR). Conclusively, prevention of hypertension and LV hypertrophy development by losartan was unrelated to cardiac or renal expression of Mas. Increased renal Ace2, and its further increase by losartan suggests the influence of locally generated Ang-(1-7) in organ response to the developing hypertension in SHRs.

Authors+Show Affiliations

Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.Department of Cardiovascular Diseases, International Clinical Research Centre, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic.Institute of Normal and Pathological Physiology, Centre of Excellence for Cardiovascular Research, Slovak Academy of Sciences, Bratislava, Slovakia.Institute of Normal and Pathological Physiology, Centre of Excellence for Cardiovascular Research, Slovak Academy of Sciences, Bratislava, Slovakia.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25766467

Citation

Klimas, Jan, et al. "Perinatally Administered Losartan Augments Renal ACE2 Expression but Not Cardiac or Renal Mas Receptor in Spontaneously Hypertensive Rats." Journal of Cellular and Molecular Medicine, vol. 19, no. 8, 2015, pp. 1965-74.
Klimas J, Olvedy M, Ochodnicka-Mackovicova K, et al. Perinatally administered losartan augments renal ACE2 expression but not cardiac or renal Mas receptor in spontaneously hypertensive rats. J Cell Mol Med. 2015;19(8):1965-74.
Klimas, J., Olvedy, M., Ochodnicka-Mackovicova, K., Kruzliak, P., Cacanyiova, S., Kristek, F., Krenek, P., & Ochodnicky, P. (2015). Perinatally administered losartan augments renal ACE2 expression but not cardiac or renal Mas receptor in spontaneously hypertensive rats. Journal of Cellular and Molecular Medicine, 19(8), 1965-74. https://doi.org/10.1111/jcmm.12573
Klimas J, et al. Perinatally Administered Losartan Augments Renal ACE2 Expression but Not Cardiac or Renal Mas Receptor in Spontaneously Hypertensive Rats. J Cell Mol Med. 2015;19(8):1965-74. PubMed PMID: 25766467.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Perinatally administered losartan augments renal ACE2 expression but not cardiac or renal Mas receptor in spontaneously hypertensive rats. AU - Klimas,Jan, AU - Olvedy,Michael, AU - Ochodnicka-Mackovicova,Katarina, AU - Kruzliak,Peter, AU - Cacanyiova,Sona, AU - Kristek,Frantisek, AU - Krenek,Peter, AU - Ochodnicky,Peter, Y1 - 2015/03/12/ PY - 2014/12/17/received PY - 2015/02/04/accepted PY - 2015/3/14/entrez PY - 2015/3/15/pubmed PY - 2016/2/24/medline KW - ACE2/Ang-(1-7)/Mas receptor axis KW - gene expression KW - hypertension KW - losartan KW - treatment KW - ventricular hypertrophy SP - 1965 EP - 74 JF - Journal of cellular and molecular medicine JO - J Cell Mol Med VL - 19 IS - 8 N2 - Since the identification of the alternative angiotensin converting enzyme (ACE)2/Ang-(1-7)/Mas receptor axis, renin-angiotensin system (RAS) is a new complex target for a pharmacological intervention. We investigated the expression of RAS components in the heart and kidney during the development of hypertension and its perinatal treatment with losartan in young spontaneously hypertensive rats (SHR). Expressions of RAS genes were studied by the RT-PCR in the left ventricle and kidney of rats: normotensive Wistar, untreated SHR, SHR treated with losartan since perinatal period until week 9 of age (20 mg/kg/day) and SHR treated with losartan only until week 4 of age and discontinued until week 9. In the hypertrophied left ventricle of SHR, cardiac expressions of Ace and Mas were decreased while those of AT1 receptor (Agtr1a) and Ace2 were unchanged. Continuous losartan administration reduced LV weight (0.43 ± 0.02; P < 0.05 versus SHR) but did not influence altered cardiac RAS expression. Increased blood pressure in SHR (149 ± 2 in SHR versus 109 ± 2 mmHg in Wistar; P < 0.05) was associated with a lower renal expressions of renin, Agtr1a and Mas and with an increase in ACE2. Continuous losartan administration lowered blood pressure to control levels (105 ± 3 mmHg; P < 0.05 versus SHR), however, only renal renin and ACE2 were significantly up-regulated (for both P < 0.05 versus SHR). Conclusively, prevention of hypertension and LV hypertrophy development by losartan was unrelated to cardiac or renal expression of Mas. Increased renal Ace2, and its further increase by losartan suggests the influence of locally generated Ang-(1-7) in organ response to the developing hypertension in SHRs. SN - 1582-4934 UR - https://www.unboundmedicine.com/medline/citation/25766467/Perinatally_administered_losartan_augments_renal_ACE2_expression_but_not_cardiac_or_renal_Mas_receptor_in_spontaneously_hypertensive_rats_ L2 - https://doi.org/10.1111/jcmm.12573 DB - PRIME DP - Unbound Medicine ER -