Table 2.
The influence of inhibitors of the renin-angiotensin-aldosterone system on ACE2
| Drugsa | Route of administration | Doseb | Durationc | Experimental animald | Tissuese | ACE2 | Ref. | ||
|---|---|---|---|---|---|---|---|---|---|
| mRNA | Protein | Activity | |||||||
| Angiotensin receptor blockers | |||||||||
| Los/(Lis) | Drinking water | 10 mg/kg/d | 12 d | Lewis rats | Heart | ↑ | − | − | 42 |
| Los/(Lis) | Drinking water | 10 mg/kg/d | 2 w | Lewis rats | Kidney | − | − | ↑ | 56 |
| Los/(Lis) | Drinking water | 10 mg/kg/d | 12 d | mRen2 tg rats | Heart/Kidney | ↑ | − | ↑ | 43 |
| Los | Drinking water | 25 mg/kg/d | 3 m | Male new Zealand white rabbits | Aorta | − | ↑ | − | 52 |
| Los | Intravenous | 2.5 mg/kg/h | – | SD rats with acute lung injury induced by LPS | Lung | − | − | ↑ | 60 |
| Los | Oral gavage | 10 or 30 mg/kg/d | – | SD rats exposed to cigarettes for 6 months | Lung | − | ↑ | − | 61 |
| Los / Olm | Subcutaneous |
Los: 10 mg/kg/d Olm: 0.1 mg/kg/d |
28 d | Lewis rats with MI induced by coronary artery ligation | Heart | ↑ | − | − | 44 |
| Olm | Subcutaneous | 0.5 mg/kg/d | 4 w | Male stroke-prone SHR | Heart/Kidney | ↑ | − | − | 45 |
| Olm | Drinking water | 10 mg/kg/d | 14 d | SHR |
Thoracic aorta Carotid artery |
↑ → |
− − |
− − |
53 |
| Azi/Olm | Oral gavage | 1 or 5 mg/kg/d | 4 w. | Male hRN/hANG-Tg mice | Heart/Kidney |
Azi↑ Olm→ |
− − |
− − |
46 |
| Tel | Oral | 10 mg/kg/d | 21 d | Lewis rats with EAM | Heart | − | ↑ | − | 47 |
| Tel | Drinking water | 2 mg/kg/d | 2 w | Female C57BLKS/J mice | Kidney (renal vasculature) | − | ↑ | − | 57 |
| Tel | Gastric gavage | 5 or 10 mg/kg/d | 10 w | Male SHR | Aorta | − | ↑ | − | 54 |
| Can/(epl) | Gastric gavage | 10 mg/kg/d | 8 w | Male DS rats | Heart | ↑ | ↑ | − | 48 |
| Epr/(spi) | Intraperitoneal | 5 mg/kg/d | 14 or 28 d | Wistar rats with experimental CHF induced by ACF | Heart | − | ↑ | ↑ | 49 |
| Irb | Drinking water | 50 mg/kg/d | 17 d | C57BL/6 mice | Aorta | ↑ | ↑ | − | 55 |
| ACE inhibitors | |||||||||
| Lis/(Los) | Drinking water | 10 mg/kg/d | 12 d | Lewis rats | Heart | ↑ | − | → | 42 |
| Lis/(Los) | Drinking water | 10 mg/kg/d | 2 w | Lewis rats | Kidney | − | − | ↑ | 56 |
| Lis/(Los) | Drinking water | 10 mg/kg/d | 12 d | mRen2 tg rats | Heart/Kidney | ↑ | − | ↑ | 43 |
| Ram | Oral | 1 mg/kg/d | 28 d | SD rats with MI induced by ligation of the left coronary artery | Heart | → | − | → | 50 |
| Ram | Gavage | 1 mg/kg/d | 10 d | Female SD rats with acute kidney injury induced by STNx. |
Kidney Plasma |
− − |
− − |
↑ ↓ |
58 |
| Per | Drinking water | 2 mg/kg/d | 5 w | Male C57bl6 mice with STZ-induced diabetes |
Kidney Plasma |
↓ − |
↓ − |
↓ ↓ |
59 |
| Ena | Gavage | 10 mg/kg/d | 8 w | SD rats with MI induced by ligation of the left coronary artery |
Heart Plasma |
↑ − |
− − |
↑ ↑ |
51 |
| Cap | Intraperitoneal | 50 mg/kg | – | SD rats with acute lung injury induced by LPS | Lung | − | ↑ | − | 62 |
| Mineralocorticoid receptor antagonists | |||||||||
| Spi | Water | 40 mg/kg/d | 4 or 11 d | SD rats with BDL as an obstructive jaundice model | Kidney | − | ↑ | − | 63 |
| Spi | Drinking water | 80 mg/kg/d | 12 w | Wistar rats with MI induced by left coronary artery ligation | Heart | − | ↑ | − | 64 |
| Spi/(Epr) | Intraperitoneal | 15 mg/kg/d | 14 or 28 d | Wistar rats with experimental CHF induced by ACF | Heart | − | ↑ | → | 49 |
| Epl/(Can) | Oral gavage | 100 mg/kg/d | 18 w | Male DS rats | Heart | → | → | − | 48 |
| Epl | Drinking water | 200 mg/kg/d | 2 w |
Patients with CHF Balb/C mice |
MΦ(h) MΦ(m) Heart(m) Kidney(m) |
↑ − ↑ → |
− − − − |
↑ ↑ ↑ → |
65 |
aLos losartan, Lis lisinopril, Olm olmesartan, Azi azilsartan, Tel telmisartan, Can candesartan, Epl eplerenone, Epr eprosartan, Spi spironolactone, Ram ramipril, Per perindopril, Ena enalapril, Cap captopril
bd day, h hour
cd day, w week, m month
dSD Sprague–Dawley, LPS lipopolysaccharide, MI myocardial infarction, SHR spontaneously hypertensive rats, EAM experimental autoimmune myocarditis, hRN/hANG-Tg human renin/ human angiotensinogen transgenic, DS Dahl salt-sensitive, CHF congestive heart failure, ACF aortocaval fistula, STNx subtotal nephrectomy, STZ streptozotocin, BDL bile duct ligation
eMΦ macrophage, h human, m mouse