Aliskiren in early postnatal life prevents hypertension and reduces asymmetric dimethylarginine in offspring exposed to maternal caloric restriction.
BACKGROUND
Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase, is involved in hypertension. We tested whether aliskiren treatment in early postnatal life can reduce ADMA and regulate the renin-angiotensin system to prevent hypertension in rat offspring exposed to maternal caloric restriction (CR).


METHODS
Four groups of 12-week-old male offspring were sacrificed: control, CR, CR+aliskiren, and CR+losartan group. The CR group included offspring from 50% food-restricted maternal rats. The CR+aliskiren and CR+losartan groups were produced by treating CR offspring with oral aliskiren 10 mg/kg/day or losartan 20 mg/kg/day between 2-4 weeks of age, respectively.


RESULTS
Blood pressure increased in CR rats, which was prevented by aliskiren or losartan. CR increased plasma ADMA levels, which aliskiren prevented. Renal renin and prorenin receptor (PRR) expression increased in CR rats treated with aliskiren, whereas both were reduced by losartan. Both aliskiren and losartan decreased renal mRNA expression of angiotensinogen, angiotensin II type 2 receptor, and Mas in CR rats. However, aliskiren increased angiotensin II type 2 receptor and Mas protein levels in CR kidneys.


CONCLUSIONS
Early aliskiren therapy prevents CR-induced hypertension via ADMA reduction, decreases angiotensinogen expression, and increases renal angiotensin II type 2 receptor and Mas protein.
Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan Master Program in Clinical Pharmacy, Kaohsiung Medical University, Taiwan.
Chien-Ning
CN
Hsu
Department of Nephrology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
Chien-Te
CT
Lee
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan.
Li-Tung
LT
Huang
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan Center for Translational Research in Biomedical Sciences, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Taiwan tainyl@hotmail.com.
You-Lin
YL
Tain
D000577:Amides / Q000494:pharmacology / Q000627:therapeutic use*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D000831:Animals, Newborn; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D031204:Caloric Restriction; D005260:Female; D005650:Fumarates / Q000494:pharmacology / Q000627:therapeutic use*; D005786:Gene Expression Regulation / Q000187:drug effects; D006655:Histone Deacetylases / Q000378:metabolism; D006973:Hypertension / Q000188:drug therapy* / Q000517:prevention & control*; D019808:Losartan / Q000494:pharmacology; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism; D017207:Rats, Sprague-Dawley
D000577:Amides; D005650:Fumarates; C446481:aliskiren; C018524:N,N-dimethylarginine; D001120:Arginine; D007703:Peptidyl-Dipeptidase A; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; D006655:Histone Deacetylases; D019808:Losartan
Aliskiren; asymmetric dimethylarginine; hypertension; nitric oxide; renin