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Evidence for a dilator function of 8-iso prostaglandin F2 alpha in rat pulmonary artery.

ABSTRACT: 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.

SUBMITTER: Jourdan KB

PROVIDER: S-EPMC1564607 | biostudies-other | 1997 Apr

REPOSITORIES: biostudies-other

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Evidence for a dilator function of 8-iso prostaglandin F2 alpha in rat pulmonary artery.

Jourdan K B KB Evans T W TW Curzen N P NP Mitchell J A JA

British journal of pharmacology 19970401 7

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 cont ...[more]

PMID: 9105703

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Project description:BACKGROUND:Lower socioeconomic status (SES) and psychosocial stress during pregnancy have been associated with adverse birth outcomes. While hypothalamic-pituitary-axis activation is thought to be the primary driver, oxidative stress may also be involved mechanistically. We used data from the Puerto Rico Testsite for Exploring Contamination Threats (PROTECT) cohort (N=476) to examine associations between self-reported psychosocial stress measures, SES indicators, and urinary oxidative stress biomarker concentrations, hypothesizing that women with lower SES and increased psychosocial stress would have elevated oxidative stress biomarkers. METHODS:Maternal age, education, marital status, insurance status, alcohol use and smoking status were obtained via self-reported questionnaires and were used as indicators of SES. Perceived stress, depression, negative life experiences, neighborhood perceptions, and social support were self-reported in questionnaires administered during pregnancy. Responses were grouped into tertiles for analysis, where the highest tertile corresponded to highest level of psychosocial stress. Urinary concentrations of 8-iso-prostaglandin F2? (8-iso-PGF2?) and its primary metabolite were measured at three study visits (median 18, 24, 28 weeks gestation) and averaged to reflect oxidative stress across pregnancy. Linear models were used to examine associations between SES indicators, tertiles of psychosocial stress and oxidative stress biomarkers. RESULTS:Average levels of 8-iso-PGF2? and the 8-iso-PGF2? metabolite were higher among pregnant women who were younger, who had public compared to private insurance, and who were unemployed compared to employed. However, no associations were observed between psychosocial stress measures and biomarker concentrations in adjusted analyses. CONCLUSIONS:Psychosocial stress during pregnancy, as indicated by self-reported questionnaire measures, was not associated with biomarkers of oxidative stress in the PROTECT study. However, results suggest that these biomarkers are elevated among women of lower SES, which is typically associated with stress. Notably, compared to other populations, self-reported psychosocial stress measures were lower in PROTECT compared to other populations.

Project description:BackgroundThe corpus luteum (CL) is a transient endocrine gland and prostaglandin F2-alpha is considered to be the principal luteolysin in pigs. In this species, the in vivo administration of prostaglandin F2-alpha induces apoptosis in large vessels as early as 6 hours after administration. The presence of the prostaglandin F2-alpha receptor (FPr) on the microvascular endothelial cells (pCL-MVECs) of the porcine corpus luteum has not yet been defined. The aim of the study was to assess FPr expression in pCL-MVECs in the early and mid-luteal phases (EL-p, ML-p), and during pregnancy (P-p). Moreover, the effectiveness of prostaglandin F2-alpha treatment in inducing pCL-MVEC apoptosis was tested.MethodsPorcine CLs were collected in the EL and ML phases and during P-p. All CLs from each animal were minced together and the homogenates underwent enzymatic digestion. The pCL-MVECs were then positively selected by an immunomagnetic separation protocol using Dynabeads coated with anti-CD31 monoclonal antibody and seeded in flasks in the presence of EGM 2-MV (Microvascular Endothelial Cell Medium-2). After 4 days of culture, the cells underwent additional immunomagnetic selection and were seeded in flasks until the confluent stage.PCR Real time, western blot and immunodetection assays were utilized to assess the presence of FPr on pCL-MVEC primary cultures. Furthermore, the influence of culture time (freshly isolated, cultured overnight and at confluence) and hormonal treatment (P4 and E2) on FPr expression in pCL-MVECs was also investigated. Apoptosis was detected by TUNEL assay of pCL-MVECs exposed to prostaglandin F2-alpha.ResultsWe obtained primary cultures of pCL-MVECs from all animals. FPr mRNA and protein levels showed the highest value (ANOVA) in CL-MVECs derived from the early-luteal phase. Moreover, freshly isolated MVECs showed a higher FPr mRNA value than those cultured overnight and confluent cells (ANOVA). prostaglandin F2-alpha treatment failed to induce an apoptotic response in all the pCL-MVEC cultures.ConclusionOur data showing the presence of FPr on MVECs and the inability of prostaglandin F2-alpha to evoke an in vitro apoptotic response suggest that other molecules or mechanisms must be considered in order to explain the in vivo direct pro-apoptotic effect of prostaglandin F2-alpha at the endothelial level.

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Evidence for a dilator function of 8-iso prostaglandin F2 alpha in rat pulmonary artery.

Publications

Evidence for a dilator function of 8-iso prostaglandin F2 alpha in rat pulmonary artery.

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