PMID- 15297265
OWN - NLM
STAT- MEDLINE
DCOM- 20050302
LR  - 20200930
IS  - 0363-6119 (Print)
IS  - 0363-6119 (Linking)
VI  - 288
IP  - 1
DP  - 2005 Jan
TI  - Simultaneous imaging of [Ca2+]i and intracellular NO production in freshly 
      isolated uterine artery endothelial cells: effects of ovarian cycle and 
      pregnancy.
PG  - R140-8
AB  - Pregnancy and the follicular phase of the ovarian cycle show elevation of uterine 
      blood flow and associated increases in uterine artery endothelium (UAE) 
      endothelial nitric oxide (NO) synthase (eNOS) expression. Nonetheless, a role for 
      increased NO production during pregnancy and the follicular phase has only been 
      inferred by indirect measures. The recent development of a uterine artery 
      endothelial cell model further suggests that pregnancy is associated with 
      reprogramming of cell signaling, such that eNOS may become more Ca(2+) sensitive 
      and be subject to regulation by Ca(2+)-independent kinases. This study describes 
      for the first time the direct and simultaneous monitoring of NO production and 
      intracellular free Ca(2+) concentration ([Ca(2+)](i)) in freshly isolated UAE 
      from pregnant, follicular, and luteal sheep. The pharmacological agonists 
      ionomycin (calcium ionophore) and thapsigargin (TG; endoplasmic reticulum Ca(2+) 
      pump inhibitor) were used to maximally elevate [Ca(2+)](i) and fully activate 
      eNOS as a measure of eNOS expression. NO production stimulated by ionomycin (5 
      microM) and TG (10 microM) were 1.95- and 2.05-fold, respectively, in 
      pregnant-UAE and 1.34- and 1.37-fold in follicular-UAE compared with luteal-UAE. 
      In contrast, the physiological agonist ATP (100 microM) stimulated a 3.43-fold 
      increase in NO in pregnant-UAE and a 1.90-fold increase in follicular-UAE 
      compared with luteal-UAE, suggesting that pregnancy and follicular phase enhance 
      eNOS activation beyond changes in expression in vivo. 2-aminoethoxydiphenyl 
      borate (APB; an inositol 1,4,5-trisphosphate receptor blocker) totally prevented 
      the ATP-induced [Ca(2+)](i) response but only partially inhibited NO production. 
      Thus pregnancy-enhanced eNOS activation in UAE is mediated through 
      [Ca(2+)](i)-insensitive pathways as well as through a greater eNOS sensitivity to 
      [Ca(2+)](i).
FAU - Yi, Fu-Xian
AU  - Yi FX
AD  - University Wisconsin-Madison, Department Obstetrics & Gynecology, Perinatal 
      Research Laboratories, 7E Meriter Hospital/Park, 202 South Park St., Madison, WI 
      53715, USA.
FAU - Magness, Ronald R
AU  - Magness RR
FAU - Bird, Ian M
AU  - Bird IM
LA  - eng
GR  - HD-33255/HD/NICHD NIH HHS/United States
GR  - HD-38843/HD/NICHD NIH HHS/United States
GR  - HL-49210/HL/NHLBI NIH HHS/United States
GR  - HL-64601/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20040805
PL  - United States
TA  - Am J Physiol Regul Integr Comp Physiol
JT  - American journal of physiology. Regulatory, integrative and comparative 
      physiology
JID - 100901230
RN  - 0 (Boron Compounds)
RN  - 0 (Calcium Channels)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (Ionophores)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 56092-81-0 (Ionomycin)
RN  - 67526-95-8 (Thapsigargin)
RN  - 8L70Q75FXE (Adenosine Triphosphate)
RN  - E4ES684O93 (2-aminoethoxydiphenyl borate)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 7.2.2.10 (Calcium-Transporting ATPases)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Adenosine Triphosphate/pharmacology
MH  - Animals
MH  - Arteries/physiology
MH  - Boron Compounds/pharmacology
MH  - Calcium/*physiology
MH  - Calcium Channels
MH  - Calcium-Transporting ATPases/antagonists & inhibitors
MH  - Endothelium, Vascular/metabolism
MH  - Estrous Cycle/*physiology
MH  - Female
MH  - Inositol 1,4,5-Trisphosphate Receptors
MH  - Ionomycin/pharmacology
MH  - Ionophores/pharmacology
MH  - Nitric Oxide/*biosynthesis
MH  - Nitric Oxide Synthase/metabolism
MH  - Nitric Oxide Synthase Type III
MH  - Pregnancy
MH  - Pregnancy, Animal/*physiology
MH  - Receptors, Cytoplasmic and Nuclear/antagonists & inhibitors
MH  - Sheep
MH  - Thapsigargin/pharmacology
MH  - Uterus/*blood supply/drug effects/physiology
EDAT- 2004/08/07 05:00
MHDA- 2005/03/03 09:00
CRDT- 2004/08/07 05:00
PHST- 2004/08/07 05:00 [pubmed]
PHST- 2005/03/03 09:00 [medline]
PHST- 2004/08/07 05:00 [entrez]
AID - 00302.2004 [pii]
AID - 10.1152/ajpregu.00302.2004 [doi]
PST - ppublish
SO  - Am J Physiol Regul Integr Comp Physiol. 2005 Jan;288(1):R140-8. doi: 
      10.1152/ajpregu.00302.2004. Epub 2004 Aug 5.