PMID- 33710923
OWN - NLM
STAT- MEDLINE
DCOM- 20210723
LR  - 20220503
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 320
IP  - 5
DP  - 2021 May 1
TI  - Impact of hyperleptinemia during placental ischemia-induced hypertension in 
      pregnant rats.
PG  - H1949-H1958
LID - 10.1152/ajpheart.00724.2019 [doi]
AB  - The prevalence of preeclampsia and obesity have increased. Although obesity is a 
      major risk factor for preeclampsia, the mechanisms linking these morbidities are 
      poorly understood. Circulating leptin levels increase in proportion to fat mass. 
      Infusion of this adipokine elicits hypertension in nonpregnant rats, but less is 
      known about how hyperleptinemia impacts blood pressure during placental ischemia, 
      an initiating event in the pathophysiology of hypertension in preeclampsia. We 
      tested the hypothesis that hyperleptinemia during reduced uterine perfusion 
      pressure (RUPP) exaggerates placental ischemia-induced hypertension. On 
      gestational day (GD) 14, Sprague-Dawley rats were implanted with osmotic 
      mini-pumps delivering recombinant rat leptin (1 microg/kg/min iv) or vehicle 
      concurrently with the RUPP procedure to induce placental ischemia or Sham. On GD 
      19, plasma leptin was elevated in Sham + Leptin and RUPP + Leptin. Leptin 
      infusion did not significantly impact mean arterial pressure (MAP) in Sham. MAP 
      was increased in RUPP + Vehicle vs. Sham + Vehicle. In contrast to our 
      hypothesis, placental ischemia-induced hypertension was attenuated by leptin 
      infusion. To examine potential mechanisms for attenuation of RUPP-induced 
      hypertension during hyperleptinemia, endothelial-dependent vasorelaxation to 
      acetylcholine was similar between Sham and RUPP; however, endothelial-independent 
      vasorelaxation to the nitric oxide (NO)-donor, sodium nitroprusside, was 
      increased in Sham and RUPP. These findings suggest that NO/cyclic guanosine 
      monophosphate (cGMP) signaling was increased in the presence of hyperleptinemia. 
      Plasma cGMP was elevated in Sham and RUPP hyperleptinemic groups compared with 
      vehicle groups but plasma and vascular NO metabolites were reduced. These data 
      suggest that hyperleptinemia during placental ischemia attenuates hypertension by 
      compensatory increases in NO/cGMP signaling.NEW & NOTEWORTHY Ours is the first 
      study to examine the impact of hyperleptinemia on the development of placental 
      ischemia-induced hypertension using an experimental animal model.
FAU - Palei, Ana C
AU  - Palei AC
AD  - Department of Surgery, The University of Mississippi Medical Center, Jackson, 
      Mississippi.
FAU - Martin, Hunter L
AU  - Martin HL
AD  - Department of Surgery, The University of Mississippi Medical Center, Jackson, 
      Mississippi.
AD  - Department of Physiology and Biophysics, The University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Wilson, Barbara A
AU  - Wilson BA
AD  - Department of Surgery, The University of Mississippi Medical Center, Jackson, 
      Mississippi.
FAU - Anderson, Christopher D
AU  - Anderson CD
AD  - Department of Surgery, The University of Mississippi Medical Center, Jackson, 
      Mississippi.
FAU - Granger, Joey P
AU  - Granger JP
AD  - Department of Physiology and Biophysics, The University of Mississippi Medical 
      Center, Jackson, Mississippi.
FAU - Spradley, Frank T
AU  - Spradley FT
AUID- ORCID: 0000-0003-3293-2753
AD  - Department of Surgery, The University of Mississippi Medical Center, Jackson, 
      Mississippi.
AD  - Department of Physiology and Biophysics, The University of Mississippi Medical 
      Center, Jackson, Mississippi.
LA  - eng
GR  - K99 HL130577/HL/NHLBI NIH HHS/United States
GR  - P20 GM104357/GM/NIGMS NIH HHS/United States
GR  - R00 HL130577/HL/NHLBI NIH HHS/United States
GR  - P20 GM121334/GM/NIGMS NIH HHS/United States
GR  - U54 GM115428/GM/NIGMS NIH HHS/United States
GR  - P01 HL051971/HL/NHLBI NIH HHS/United States
GR  - T32 HL105324/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20210312
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Leptin)
SB  - IM
MH  - Animals
MH  - Blood Pressure/physiology
MH  - Female
MH  - Heart Rate/physiology
MH  - Hypertension/*physiopathology
MH  - Leptin/*blood/pharmacology
MH  - Placenta/*blood supply/drug effects
MH  - Placental Insufficiency/*physiopathology
MH  - Pre-Eclampsia/physiopathology
MH  - Pregnancy
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC8163645
OTO - NOTNLM
OT  - RUPP
OT  - blood pressure
OT  - blood vessel
OT  - obesity
OT  - women's health
COIS- No conflicts of interest, financial or otherwise, are declared by the authors.
EDAT- 2021/03/13 06:00
MHDA- 2021/07/24 06:00
PMCR- 2022/05/01
CRDT- 2021/03/12 17:11
PHST- 2021/03/13 06:00 [pubmed]
PHST- 2021/07/24 06:00 [medline]
PHST- 2021/03/12 17:11 [entrez]
PHST- 2022/05/01 00:00 [pmc-release]
AID - H-00724-2019 [pii]
AID - 10.1152/ajpheart.00724.2019 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2021 May 1;320(5):H1949-H1958. doi: 
      10.1152/ajpheart.00724.2019. Epub 2021 Mar 12.