PMID- 9105703
OWN - NLM
STAT- MEDLINE
DCOM- 19970624
LR  - 20161019
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 120
IP  - 7
DP  - 1997 Apr
TI  - Evidence for a dilator function of 8-iso prostaglandin F2 alpha in rat pulmonary 
      artery.
PG  - 1280-5
AB  - 1. 8-Iso prostaglandin F2 alpha (8-iso PGF2 alpha) is one of a series of 
      prostanoids formed independently of the cyclo-oxygenase pathway. It has been 
      shown to be upregulated in many conditions of oxidant stress where its formation 
      is induced by free radical-catalysed actions on arachidonic acid. As 8-iso PGF2 
      alpha is formed in vivo in diseases in which oxidant stress is high such as 
      septic shock, we have assessed the relative potency and efficacy of this compound 
      in pulmonary arteries from control and lipopolysaccharide (LPS)-treated rats. 2. 
      Several studies have characterized the contractile actions of 8-iso PGF2 alpha on 
      various smooth muscle preparations, but its potential dilator actions have not 
      been addressed. Thus these studies examined both the contractile and dilator 
      actions of 8-iso PGF2 alpha in rat pulmonary artery rings. The thromboxane 
      mimetic U46619, PGE2 sodium nitroprusside (SNP) and acetyl choline (ACh) were 
      used for comparison. Each prostanoid had to be dissolved in ethanol to a maximum 
      concentration of 1 x 10-2 M. At high concentrations, ethanol directly contracted 
      pulmonary vessels. We were therefore limited by the actions of the vehicle such 
      that we were unable to add prostanoids at concentrations higher than 1 x 10-4 M. 
      In some cases this meant that maximum responses were not achieved and in these 
      cases the Emax and pD2 values are apparent estimates. 3. The following rank order 
      of potency was obtained from contractile studies; U46619 > 8-iso PGF2 alpha > 
      PGE2, each prostanoid producing concentration-dependent contractions (10(-10)-3 x 
      10(-4) M, 10(-9)-10(-4) M, 10(-8)-10(-4) M, respectively). As has been shown 
      previously for other smooth muscle preparations, the thromboxane receptor (TP) 
      antagonist ICI 192605, (1 x 10(-6), 1 x 10(-5) and 1 x 10(-4) M), inhibited the 
      contractions of 8-iso PGF2 alpha in a concentration-dependent fashion. 4. The 
      nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (L-NAME; 1 x 
      10(-4) M), enhanced the contractile function of both 8-iso PGF2 alpha and PGE2, 
      but had no effect on that caused by U46619. Similarly, L-NAME inhibited the 
      dilator function of all agents tested except the exogenous nitric oxide (NO) 
      donor SNP indicating that PGE2 and 8-iso PGF2 alpha like ACh, act through the 
      release of NO. The specificity of the effects of L-NAME were confirmed in studies 
      with the inactive enantiomer D-NAME (1 x 10(-4) M), which did not affect the 
      contractile or the dilator actions of 8-iso PGF2 alpha. Furthermore, ICI 192605 
      enhanced the dilator actions of 8-iso PGF2 alpha, suggesting that the dilator 
      component of 8-iso PGF2 alpha was achieved via activation of a non-TP receptor. 
      5. Isoprostanes may modulate vascular tone by a direct action on TP receptors to 
      cause contraction and via a distinct receptor leading to the release of NO to 
      cause dilation.
FAU - Jourdan, K B
AU  - Jourdan KB
AD  - Unit of Critical Care Medicine, Royal Brompton Hospital, London.
FAU - Evans, T W
AU  - Evans TW
FAU - Curzen, N P
AU  - Curzen NP
FAU - Mitchell, J A
AU  - Mitchell JA
LA  - eng
GR  - Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Dioxanes)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (F2-Isoprostanes)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Prostaglandin Endoperoxides, Synthetic)
RN  - 0 (Vasodilator Agents)
RN  - 117621-64-4 (ICI 192605)
RN  - 27415-26-5 (8-epi-prostaglandin F2alpha)
RN  - 57576-52-0 (Thromboxane A2)
RN  - 76898-47-0 (15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid)
RN  - B7IN85G1HY (Dinoprost)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - V55S2QJN2X (NG-Nitroarginine Methyl Ester)
RN  - XXE1CET956 (Indomethacin)
SB  - IM
MH  - 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
MH  - Animals
MH  - Dinoprost/*analogs & derivatives/pharmacology
MH  - Dinoprostone/pharmacology
MH  - Dioxanes/pharmacology
MH  - Enzyme Inhibitors/pharmacology
MH  - F2-Isoprostanes
MH  - In Vitro Techniques
MH  - Indomethacin/pharmacology
MH  - Lipopolysaccharides/pharmacology
MH  - Male
MH  - NG-Nitroarginine Methyl Ester/pharmacology
MH  - Nitric Oxide Synthase/antagonists & inhibitors
MH  - Prostaglandin Endoperoxides, Synthetic/pharmacology
MH  - Pulmonary Artery/*drug effects/physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Thromboxane A2/analogs & derivatives/pharmacology
MH  - Vasodilator Agents/*pharmacology
PMC - PMC1564607
EDAT- 1997/04/01 00:00
MHDA- 1997/04/01 00:01
PMCR- 1998/03/01
CRDT- 1997/04/01 00:00
PHST- 1997/04/01 00:00 [pubmed]
PHST- 1997/04/01 00:01 [medline]
PHST- 1997/04/01 00:00 [entrez]
PHST- 1998/03/01 00:00 [pmc-release]
AID - 0701052 [pii]
AID - 10.1038/sj.bjp.0701052 [doi]
PST - ppublish
SO  - Br J Pharmacol. 1997 Apr;120(7):1280-5. doi: 10.1038/sj.bjp.0701052.