Carbon Monoxide Releasing Molecules Blunt Placental Ischemia-Induced Hypertension.
Am J Hypertens
; 30(9): 931-937, 2017 Sep 01.
Article
in En
| MEDLINE
| ID: mdl-28472389
ABSTRACT
BACKGROUND:
Preeclampsia is a pregnancy complication which manifests as new-onset hypertension, proteinuria, and a spectrum of other symptoms. While the underlying causes are still a subject of much debate, it is commonly believed that placental ischemia is a central cause. The ischemic placenta secretes factors which are believed to be responsible for the maternal syndrome; most notably the anti-angiogenic protein soluble fms-like tyrosine kinase 1 (sFlt-1). We have reported that induction of the carbon monoxide (CO) producing protein heme oxygenase-1 restored angiogenic imbalance and reduced blood pressure in a rat model of placental ischemia, and that CO blocks hypoxia-induced sFlt-1 production from placental tissue in vitro. We therefore hypothesized that direct administration of CO by a CO-releasing molecule (CORM) would blunt the placental ischemia-induced increase in sFlt-1 and thus the hypertension characteristic of this model.METHODS:
We administered a soluble CO donor molecule (CORM-3) daily i.v. in control animals or those undergoing placental ischemia from GD14. Blood pressure and renal function were measured on GD19, and angiogenic markers measured by ELISA.RESULTS:
Interestingly, though we found that CORM administration significantly blunted the hypertensive response to placental ischemia, there was no concomitant normalization of sFlt-1 in either the placenta or maternal circulation. We did find, however, that CORM administration caused a significant increase in glomerular filtration rate, presumably by vasodilation of the renal arteries and increased renal plasma flow.CONCLUSIONS:
All in all these data suggest that administration of CO by CORMs do lower blood pressure during placental ischemia mechanisms independent of changes in angiogenic balance.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organometallic Compounds
/
Placenta
/
Pre-Eclampsia
/
Blood Pressure
/
Carbon Monoxide
/
Ischemia
/
Kidney
/
Antihypertensive Agents
Type of study:
Etiology_studies
/
Prognostic_studies
Limits:
Animals
/
Pregnancy
Language:
En
Journal:
Am J Hypertens
Journal subject:
ANGIOLOGIA
Year:
2017
Document type:
Article
Affiliation country:
United States