title: A complicated role for the renin-angiotensin system during pregnancy: highlighting the importance of drug discovery.
abstract: BACKGROUND
  Blood pressure management is recommended to avoid maternal cerebrovascular or cardiovascular compromise during pregnancy. Current antihypertensive treatment during pregnancy with positive safety profiles includes labetalol, hydralazine, methyldopa and nifedipine.
  
  
  METHODS
  Many earlier animal and human studies indicate that angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) are associated with fetopathy; therefore, these drugs are contraindicated during pregnancy, especially if these medications were taken during the second and third trimesters. The role of the RAS is quite complex, with fetal development heavily dependent on its appropriate expression and function. New findings indicate that the placental unit expresses its own RAS in order to regulate angiogenesis. Multiple studies have shown that women with abnormal uterine doppler sonography produce an agonistic autoantibody to the angiotensin I receptor, implicating a role for RAS function and regulation in abnormal pregnancies. Importantly, interruption of a normal RAS compromises fetal development.
  
  
  CONCLUSIONS
  Traditional medications that inhibit components of RAS for long-term hypertension control are not appropriate for use before or during pregnancy. Further study and drug discovery are needed to find alternative pathways for treatment of hypertensive disorders when pregnancy is present or a possibility.
authors.affiliation: University of Mississippi Medical Center, Departments of Obstetrics & Gynecology , 2500 North State Street, Jackson MS 39216 , USA +1 601 984 5358 ; mmdarby@umc.edu.
authors.forename: Marie
authors.initials: M
authors.lastname: Darby
authors.forename: James N
authors.initials: JN
authors.lastname: Martin
authors.forename: Babbette
authors.initials: B
authors.lastname: LaMarca
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D015195:Drug Design; D055808:Drug Discovery; D005260:Female; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D011247:Pregnancy; D011249:Pregnancy Complications, Cardiovascular / Q000188:drug therapy* / Q000503:physiopathology; D012084:Renin-Angiotensin System / Q000187:drug effects
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents