Table 2.

Interventions targeting on the RAAS to prevent hypertension and kidney disease of developmental origins.Studies tabulated according to types of intervention, animal model, species, and age at evaluation. SD, Sprague Dawley; SHR, spontaneously hypertensive rat; M, male; F, female; ACE2, angiotensin-converting enzyme 2; AGT, angiotensinogen; Ang II, angiotensin II; AT1R, angiotensin type 1 receptor; MAS receptor, ANG-(1–7) receptor MAS.

Intervention	Animal Model	Species/Gender	Age at Evaluation	Effects	Protective Mechanism	Ref.
Renin inhibitor
Aliskiren (10 or 30 mg/kg/day) between 4–10 weeks of age	Genetic hypertension model	SHR/M	10 weeks	Prevented or attenuated hypertension by 30 or 10 mg, respectively	Restoration of NO bioavailability	[118]
Aliskiren (10 mg/kg/day) between 2–4 weeks of age	Maternal 50% caloric restriction	SD rat/M	12 weeks	Prevented hypertension	Decreased renal AGT mRNA; Increased renal ACE2 and MAS receptor protein levels	[119]
Aliskiren (10 mg/kg/day) between 2–4 weeks of age	Maternal high-fructose diet	SD rat/M and F	12 weeks	Prevented hypertension in both sexes	Increased renal ACE2 and MAS receptor protein levels in F	[52]
ACEI
Captopril (100 mg/kg/day) between 2–4 weeks of age	Maternal protein restriction	Wistar rat/M	12 weeks	Prevented hypertension	Not evaluated	[63]
Captopril (100 mg/kg b.w./day) between 4–10 weeks of age	Genetic hypertension model	SHR/M	30 weeks	Attenuated hypertension	Not evaluated	[147]
Enalapril (100 mg/L) in drinking water between 3–6 weeks of age	Maternal protein restriction	SD rat/M	16 weeks	Prevented hypertension	Not evaluated	[148]
Enalapril (100 mg/L) in drinking water between 3–6 weeks of age	Maternal protein restriction	SD rat/M	6 months	Prevented hypertension and albuminuria	Reduced urinary AGT and ANG II levels	[149]
Perindopril (3 mg/kg/day) between 4–16 weeks of age	Genetic hypertension model	SHR/M	28 weeks	Attenuated hypertension and renal dysfunction	Not evaluated	[150]
ARB
Losartan (100 mg/L) in drinking water between 2–4 weeks of age	Maternal protein restriction	Wistar rat/M	12 weeks	Prevented hypertension	Not evaluated	[151]
Losartan (20 mg/kg/day) between 2–4 weeks of age	Maternal 50% caloric restriction	SD rat/M	12 weeks	Prevented hypertension	Decreased renal AGT mRNA	[118]
Losartan (20 mg/kg/day) between 4–9 weeks of age	Genetic hypertension model	SHR/M	9 weeks	Prevented hypertension	Increased renal ACE2 expression	[152]
AT1R antisense
AT1R antisense delivery at 5 days of age	Genetic hypertension model	SHR/M	3 months	Prevented hypertension	Decreased AT1R mRNA	[153]
ACE2 activator
Diminazene aceturate in pregnancy	Maternal hypertension	SHR/M	16 weeks	Attenuated hypertension and renal fibrosis	Not evaluated in the kidney	[154]
ANG-(1-7) in pregnancy	Maternal hypertension	SHR/M	16 weeks	Attenuated hypertension and renal fibrosis	Not evaluated in the kidney	[154]