Table 2.
Representative Animal Models of HTN-Preg
| Model / Species |
Technique | Manifestations | Other PE-Relevant Findings |
Ref | |||
|---|---|---|---|---|---|---|---|
| BP (mmHg) |
Proteinuria (mg/24hr) |
Pup Weight (g) |
Litter size (# of pups) |
Norm-Preg vs. HTN-Preg | |||
| RUPP Sprague- Dawley Rat |
Two groups: Norm-Preg RUPP On gestation day 14, a silver clip (0.203mm ID) is placed around the abdominal aorta and another clip (0.1mm ID) is placed on the main uterine branches of the ovarian arteries. |
99±3 132±4 |
n/a |
3.2±0.1 1.76± ±.08 |
12.7±0.5 7.7±1.3 |
sFlt-1 ~70 vs. ~675pg/ml TNF-α ~8 vs. ~18pg/ml. sEng 0.10±0.02 vs. 0.05±0.01 apu HIF-α 1.42±0.25 vs. 0.68±0.09 apu Hemeoxygenase (HO-1) 1.4±0.3 vs. 2.5±0.1 apu Bradykinin relaxation 62±2 vs. 40±2% Ach relaxation 92±1 vs. 70±3% Cardiac output 65±5 vs. 104 ±7 ml/min. Cardiac index (CI) 348±19 vs. 246 ±20 ml/min. Total peripheral resistance 0.98±0.08 vs. 2.15±0.02 mmHg/ml/min |
[7,77 –79] |
| TNF-α, IL- 6 Sprague- Dawley Rat |
Two Groups: Norm-Preg Cytokine-infused On gestation day 14, rats are infused iv with TNF-αor I L-6 200ng/kg/day for 5 days. |
96±3 123±3 |
15.6±2.4 88.2±9.6 |
10.4±0.6 2.6±0.2 |
10.4±0.6 7.3±0.5 |
Cytokine-infused pregnant rats show increased vascular responses to vasoconstrictors and inhibition of endothelium- dependent NO-cGMP vascular relaxation. |
[80] |
| L-NAME Treated Sprague- Dawley Rat |
Four groups: Virgin Virgin+L-NAME Preg Preg+L-NAME On gestation day 15, pregnant and virgin rats received L- NAME4 mg/kg/day in drinking water. |
118±3 125±6 113±5 172±6 |
n/a |
n/a |
n/a |
Reduction of NO production in late pregnancy is associated with increased contraction and [Ca2+]I in VSM and may lead to the increased vascular resistance associated with HTN-Preg. |
[81,82] |
| DOCA- Treated pregnant Sprague- Dawley Rat |
Five Groups: Virgin Preg Preg+DOCA Preg+DOCA+MMF Preg+DOCA+AZA |
106±2 116±4 133±4 112±6 122±2 |
Urinary Albumin/Cr (mg/mg;% of control) 100±48 91±23 369±47 121±31 169±36 |
Litter # - 14.0±0.6 10.2±0.7 17.1±0.3 13.2±0.8 |
Malformed Litter # - 0.0±0.0 1.0± 0.3 17.1±0.3 3.9±1.5 |
Serum Th1-type cytokines IL-2 , I L-12, IFNγ, and RANTES were elevated in HTN-Preg rats. Th2-type cytokine I L-4 was elevated in Norm-Preg rats. MMF attenuated the HTN, proteinuria, and endothelial dysfunction and the increased proinflammatory Th1 cytokine profile in preg rats treated with DOCA/salt |
[8] |
| 2-ME Deficient Mouse |
Four groups: COMT+/+ COMT+/++RO41- 0960 (COMT inhibitor , S Q , 24 mg/kg/day) COMT−/− COMT −/− + 2-ME (SQ, 10 ng/day) |
105 122 121 108 |
Albumin/Cr 1.0 1.48 1.50 1.20 |
Placenta Weight 0.094 0.085 0.085 0.090 |
# Dead embryos 1 - 2.5 1 |
Decreased levels of 2-ME are associated with symptoms of PE. 2-ME may have utility as a plasma and urine diagnostic marker of PE, and may serve as a therapeutic supplement to prevent or treat PE. |
[83] |
apu, arbitrary pixel unit; n/a, not available; AZA, azathioprine (immunosuppressant); DOCA, deoxycorticosterone acetate; MMF, mycophenolate mofetil (immunosuppressant); 2-ME, 2- methoxy estradiol, COMT, catechol-O-methyl transferase