PMID- 24159378
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211021
IS  - 2051-817X (Print)
IS  - 2051-817X (Electronic)
IS  - 2051-817X (Linking)
VI  - 1
IP  - 4
DP  - 2013 Sep 1
TI  - Obese melanocortin-4 receptor-deficient rats exhibit augmented angiogenic balance 
      and vasorelaxation during pregnancy.
PG  - e00081
LID - e00081
AB  - While obesity is a major risk factor for preeclampsia, the mechanisms linking 
      obesity and hypertension during preeclampsia remain unclear. Hypertension in 
      preeclampsia is associated with placental ischemia-induced release of 
      anti-angiogenic soluble fms-like tyrosine kinase (sFlt-1) into the maternal 
      circulation, which antagonizes vascular endothelial growth factor (VEGF) 
      promoting endothelial dysfunction. Haploinsufficiency, defined as loss of one 
      copy of a gene via a mutation, of the melanocortin-4 receptor (MC4R) is the most 
      common cause of monogenetic obesity in humans. The purpose of our study was to 
      determine the effects of genetic obesity on angiogenic balance, endothelial 
      function, and blood pressure in pregnant MC4R+/- and MC4R+/+ rats. At gestational 
      day (GD) 18, body weight and total body fat mass were greater in MC4R+/- than 
      MC4R+/+ rats. On GD 19, plasma sFlt-1 was not significantly different between 
      groups. Interestingly, circulating VEGF was greater in the obese rats with the 
      source being adipose tissue and not the placenta. Wire myography showed in 
      third-order mesenteric arteries that sensitivity (logEC50) to endothelial 
      dependent and nitric oxide donor-induced vasorelaxation was greater in MC4R+/- 
      versus MC4R+/+. Mean arterial blood pressure was similar between groups. In 
      conclusion, under normal pregnant conditions, genetically obese pregnant animals 
      have greater angiogenic balance and dependency of vasorelaxation on nitric oxide 
      signaling protecting against the development of hypertension. However, we 
      speculate that, in the face of reduced uterine perfusion, a rise in circulating 
      placental factors that target and reduce nitric oxide bioavailability exposes the 
      susceptibility of genetically obese animals to greater hypertension in pregnancy.
FAU - Spradley, Frank T
AU  - Spradley FT
AD  - Department of Physiology and Biophysics, Cardiovascular-Renal Research Center, 
      University of Mississippi Medical Center, Jackson, MS 39216.
FAU - Palei, Ana C
AU  - Palei AC
FAU - Granger, Joey P
AU  - Granger JP
LA  - eng
GR  - P01 HL051971/HL/NHLBI NIH HHS/United States
GR  - T32 HL105324/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PL  - United States
TA  - Physiol Rep
JT  - Physiological reports
JID - 101607800
PMC - PMC3804345
MID - NIHMS518110
OTO - NOTNLM
OT  - Angiogenic balance
OT  - MC4R
OT  - blood pressure
OT  - obesity
OT  - pregnancy
OT  - vasorelaxation
EDAT- 2013/10/26 06:00
MHDA- 2013/10/26 06:01
PMCR- 2013/09/01
CRDT- 2013/10/26 06:00
PHST- 2013/10/26 06:00 [entrez]
PHST- 2013/10/26 06:00 [pubmed]
PHST- 2013/10/26 06:01 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - 10.1002/phy2.81 [doi]
PST - ppublish
SO  - Physiol Rep. 2013 Sep 1;1(4):e00081. doi: 10.1002/phy2.81.