Vasoconstrictor responses, and underlying mechanisms, to isoprostanes in human and porcine bronchial arterial smooth muscle

Tazzeo, Tracy; Miller, John D.; Janssen, Luke J.

doi:10.1038/sj.bjp.0705482

Cited by 38 publications

(28 citation statements)

References 22 publications

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“…There is no obvious reason why the effects of 8-iso PGF 2a were apparently different to those of 8-iso PGE 2 , but it is evident that a different mechanism for 8-iso PGE 2 exists, which operates at least in part via the Rho kinase pathway. On speculation, this difference observed in relation to antagonism with Y-27632 can only be due to a relative difference in potencies observed in tissues, whereby 8-iso-PGE 2 is more potent (Oliveira et al 2000, Tazzeo et al 2003. There are no signalling pathways to our knowledge, known to operate via 8-iso-PGE 2 and 8-iso-PGF 2a directly.…”

Section: Discussionmentioning

confidence: 87%

Rho A/Rho kinase: human umbilical artery mRNA expression in normal and pre eclamptic pregnancies and functional role in isoprostane-induced vasoconstriction

Friel¹,

Sexton²,

O’Reilly³

et al. 2006

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Pre eclampsia represents a state of increased or prolonged vasoconstriction, partially linked to the potent vasocontractile effect of isoprostanes. The process of Rho A-mediated calcium sensitisation is inherent to a state of prolonged contractility in many smooth muscle types. The aim of this study was (1) to investigate mRNA expression levels of Rho A and Rho kinase isoforms (I and II) in the umbilical artery from normotensive and pre eclamptic women and (2) to determine whether the effects of two isoprostanes, 8-iso prostaglandin F 2a (8-iso PGF2a) and 8-iso prostaglandin E 2 (8-iso PGE 2 ), on umbilical artery tone, were mediated via the Rho kinase pathway. Real-time RT-PCR using primers for Rho A, ROCK I and ROCK II was performed on total RNA isolated from umbilical artery specimens obtained from normotensive and pre eclamptic women. The effects of both isoprostanes (nZ6) (in the absence and presence of the specific Rho kinase inhibitor Y-27632), on umbilical artery tone were measured, and compared with control recordings. Rho A mRNA expression levels were significantly lower in umbilical artery samples obtained from pre eclamptic women (nZ4) in comparison to those from normotensive women (nZ6) (P!0.05). ROCK I and ROCK II mRNA levels were similar in both vessel types (PO0.05). Both isoprostanes exerted a significant concentration-dependent vasocontractile effect (nZ7) (P!0.001) on umbilical artery. For 8-iso PGE 2 , this effect was antagonised by Y-27632 (nZ6) (P!0.01). The significant reduction of Rho A mRNA levels in umbilical arteries from pregnancies complicated by pre eclampsia may serve to counteract the diminished perfusion associated with the pathophysiology of pre eclampsia. The vasocontractile effect of 8-iso PGE 2 in pre eclampsia may in part be mediated via the Rho kinase pathway.

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Section: Discussionmentioning

confidence: 87%

Rho A/Rho kinase: human umbilical artery mRNA expression in normal and pre eclamptic pregnancies and functional role in isoprostane-induced vasoconstriction

Friel¹,

Sexton²,

O’Reilly³

et al. 2006

Reproduction

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“…[99][100][101][102][103][104] Isoprostanes not only serve as biomarkers of the disease but also act as signal transduction molecules exerting multiple biological effects through prostanoid receptors and other signaling pathways. 47,[105][106][107] They can exert their effects on pulmonary vasculature in many ways, including pulmonary vasoconstriction, 48,108,109 induction of pulmonary endothelium to release endothelin 1, vasoconstriction in general, 49,110 and nonspecific effects on smooth muscle, such as hyperresponsiveness and hypertrophy, 50,51 thereby serving as important mediators in many lung pathologies including PAH.…”

Section: Role Of Lysophosphatidic Acidmentioning

confidence: 99%

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

et al. 2016

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Pulmonary arterial hypertension (PAH) is a multifactorial disease characterized by interplay of many cellular, molecular, and genetic events that lead to excessive proliferation of pulmonary cells, including smooth muscle and endothelial cells; inflammation; and extracellular matrix remodeling. Abnormal vascular changes and structural remodeling associated with PAH culminate in vasoconstriction and obstruction of pulmonary arteries, contributing to increased pulmonary vascular resistance, pulmonary hypertension, and right ventricular failure. The complex molecular mechanisms involved in the pathobiology of PAH are the limiting factors in the development of potential therapeutic interventions for PAH. Over the years, our group and others have demonstrated the critical implication of lipids in the pathogenesis of PAH. This review specifically focuses on the current understanding of the role of oxidized lipids, lipid metabolism, peroxidation, and oxidative stress in the progression of PAH. This review also discusses the relevance of apolipoprotein A-I mimetic peptides and microRNA-193, which are known to regulate the levels of oxidized lipids, as potential therapeutics in PAH.

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“…Another point of interest is that some of the F-ring isoprostanes, such as 8-iso-PGF 2␣ and 8-iso-PGF 2␤ , produced, in our experiments, levels of contraction that are comparable with those induced by the E-ring isoprostanes. In contrast, in the porcine adult pulmonary vessels, F-ring isoprostanes induced markedly weaker contractions than E-ring isoprostanes (21,26). Finally, Janssen and Tazzeo (21) observed that, although the contractions induced in adult porcine PA and PV by 8-iso-PGE 1 , 8-iso-PGF 1␣ , 8-iso-PGF 2␣ , and 8-iso-PGF 2␤ were essentially completely prevented by TP receptor blockade, 8-iso-PGE 2 was able to evoke substantial contraction of PV in the maintained presence of TP receptor blockade.…”

Section: Discussionmentioning

confidence: 92%

“…However, when compared with U46619, 8-iso-PGF 2␣ was less potent by approximately one order of magnitude (20). Janssen and Tazzeo (21) and Tazzeo et al (26) examined the responses of adult porcine PA and veins to 8-iso-PGE 1 , 8-iso-PGE 2 , 8-iso-PGF 1␣ , 8-iso-PGF 2␣ , and 8-iso-PGF 2␤ , finding that 8-iso-PGE 2 was the most potent and efficacious in both PA and veins. However, isoprostanes exerted, in adult pulmonary vessels, maximal contractions that were 50 -90% of the response to 60 mM KCl, whereas the contractions that we describe in 12-to 24-h-old and 2-wk-old tissues were as much as 150 -200% of the response to KCl.…”

Section: Discussionmentioning

confidence: 99%

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Age-Related Differences in Vasoconstrictor Responses to Isoprostanes in Piglet Pulmonary and Mesenteric Vascular Smooth Muscle

et al. 2005

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Isoprostanes are prostaglandin (PG)-like compounds produced nonenzymatically by free radical-catalyzed peroxidation of arachidonic acid. Isoprostanes evoke potent vascular effects but their actions in the neonatal vasculature are poorly known. We aimed to study the effects of 8-iso-PGE 1 , 8-iso-PGE 2 , 8-iso-PGF 1␣ , 8-iso-PGF 1␤ , 8-iso-PGF 2␣ , and 8-iso-PGF 2␤ in pulmonary arteries (PA), pulmonary veins (PV), and mesenteric arteries (MA) from newborn and 2-wk-old piglets. Isoprostanes produced concentrationdependent contractions of PA, PV, and MA (magnitudes up to 1.5-to 2-fold greater than the responses to 62.5 mM KCl) but they were markedly less potent vasoconstrictors than the thromboxane A 2 (TXA 2 ) mimetic U46619. Neonatal PA were more sensitive to 8-iso-PGF 1␣ , 8-iso-PGF 1␤ , and 8-iso-PGF 2␤ than 2-wk-old PA. Neonatal PV were more sensitive to 8-iso-PGE 2 and 8-iso-PGF 1␣, and neonatal MA were more sensitive to 8-iso-PGE 2 , 8-iso-PGF 1␣ , 8-iso-PGF 1␤ , 8-iso-PGF 2␣ , and 8-iso-PGF 2␤ than the corresponding 2-wk-old vessels. The sensitivity to U46619 decreased with postnatal age in MA but did not change in PA and PV. The contractile responses to all the isoprostanes and to U46619 were reverted by the TXA 2 receptor (TP) antagonist SQ 29,548. Moreover, isoprostaneevoked contractions in 2-wk-old PA were reduced by inhibitors of tyrosine kinase (genistein) and Rho kinase (Y 27632 and hydroxyfasudil) but not by inhibitors of protein kinase C (chelerythrine), mitogen-activated protein kinase kinase (PD 98059) or p38-kinase (SB 203580). In conclusion, isoprostanes produced compound-, tissue-, and age-dependent constriction of neonatal porcine pulmonary and mesenteric vascular smooth muscle. Isoprostanes are PG-like compounds formed in vivo by the free radical-catalyzed peroxidation of arachidonic acid, a reaction independent of the COX enzyme (1-3). They are generated initially at the site of a free radical attack of esterified arachidonate in cell membranes from which they are cleaved, presumably by phospholipases (2,3). Isoprostanes are used clinically and experimentally as markers for many disease states in which oxidative stress is a prominent feature, including asthma, myocardial and renal ischemia-reperfusion injury, atherosclerosis, pulmonary hypertension, and hypercholesterolemia (4 -6). However, isoprostanes are much more than inert markers and have been shown to possess biologic activity in whole-animal, isolated tissue, and cell-based systems (6,7). In the vascular system, isoprostanes exert important effects that range from powerful vasoconstriction to complete vasodilatation, depending on the particular isoprostane, tissue, and species studied (7).The neonatal period appears to be particularly interesting for the study of the biologic effects of isoprostanes because the

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Vasoconstrictor responses, and underlying mechanisms, to isoprostanes in human and porcine bronchial arterial smooth muscle

Cited by 38 publications

References 22 publications

Rho A/Rho kinase: human umbilical artery mRNA expression in normal and pre eclamptic pregnancies and functional role in isoprostane-induced vasoconstriction

Rho A/Rho kinase: human umbilical artery mRNA expression in normal and pre eclamptic pregnancies and functional role in isoprostane-induced vasoconstriction

Role of Oxidized Lipids in Pulmonary Arterial Hypertension

Age-Related Differences in Vasoconstrictor Responses to Isoprostanes in Piglet Pulmonary and Mesenteric Vascular Smooth Muscle

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