title: Perinatally administered losartan augments renal ACE2 expression but not cardiac or renal Mas receptor in spontaneously hypertensive rats.
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.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.
authors.forename: Jan
authors.initials: J
authors.lastname: Klimas
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.
authors.forename: Michael
authors.initials: M
authors.lastname: Olvedy
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.
authors.forename: Katarina
authors.initials: K
authors.lastname: Ochodnicka-Mackovicova
authors.affiliation: Department of Cardiovascular Diseases, International Clinical Research Centre, St. Anne's University Hospital and Masaryk University, Brno, Czech Republic.
authors.forename: Peter
authors.initials: P
authors.lastname: Kruzliak
authors.affiliation: Institute of Normal and Pathological Physiology, Centre of Excellence for Cardiovascular Research, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Sona
authors.initials: S
authors.lastname: Cacanyiova
authors.affiliation: Institute of Normal and Pathological Physiology, Centre of Excellence for Cardiovascular Research, Slovak Academy of Sciences, Bratislava, Slovakia.
authors.forename: Frantisek
authors.initials: F
authors.lastname: Kristek
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.
authors.forename: Peter
authors.initials: P
authors.lastname: Krenek
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Bratislava, Slovakia.
authors.forename: Peter
authors.initials: P
authors.lastname: Ochodnicky
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000831:Animals, Newborn; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D019808:Losartan / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011918:Rats, Inbred SHR; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D009569:Nitric Oxide; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D019808:Losartan
keywords: ACE2/Ang-(1-7)/Mas receptor axis; gene expression; hypertension; losartan; treatment; ventricular hypertrophy