This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hou, X. Articles by Ellis, E. F. Search for Related Content PubMed PubMed Citation Articles by Hou, X. Articles by Ellis, E. F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB PROSTAGLANDIN F2ALPHA Related Collections Endothelium/vascular type/nitric oxide Animal models of human disease Acute Stroke Syndromes Ischemic biology - basic studies Stroke in Children and the Young

(Stroke. 2000;31:516.)
© 2000 American Heart Association, Inc.

Original Contributions

Augmented Vasoconstriction and Thromboxane Formation by 15-F_2t-Isoprostane (8-Iso-Prostaglandin F₂) in Immature Pig Periventricular Brain Microvessels

Xin Hou, MD, PhD; Fernand Gobeil, Jr, PhD; Krishna Peri, PhD; Giovanna Speranza, BSc; Anne Marilise Marrache, BSc; Pierre Lachapelle, PhD; Jackson Roberts, II, MD; Daya R. Varma, MD, PhD Sylvain Chemtob, MD, PhD

From the Centre de Recherche de l’Hôpital Sainte-Justine, Department of Pediatrics and Pharmacology, Université de Montréal, Montréal, Québec, Canada (X.H., F.G., K.P., G.S., A.M.M., S.C.); Departments of Pharmacology and Therapeutics (G.S., A.M.M., D.R.V., S.C.) and Ophthalmology (P.L.), McGill University, Montréal, Québec, Canada; and Departments of Pharmacology and Medicine, Vanderbilt University, Nashville, Tenn (J.R.).

Correspondence to Sylvain Chemtob, MD, PhD, Research Center, Hôpital Sainte-Justine, Department of Pediatrics and Pharmacology, 3175 Côte Sainte-Catherine, Montréal, Québec, Canada, H3T 1C5. E-mail chemtobs{at}ere.umontreal.ca

Background and Purpose—Oxidant stress, especially in the premature, plays a major role in the pathogenesis of hypoxic-ischemic encephalopathies mostly manifested in the periventricular region. We studied the vasomotor mode of actions of the peroxidation product 15-F_2t-isoprostane (15-F_2t-IsoP) (8-iso-prostaglandin F₂) on periventricular region during development.

Methods—Effects of 15-F_2t-IsoP on periventricular microvessels of fetal, newborn, and juvenile pigs were studied by video imaging and digital analysis techniques. Thromboxane formation and intracellular Ca²⁺ were measured by radioimmunoassay and by using the fluorescent indicator fura 2-AM.

Results—15-F_2t-IsoP–mediated constriction of periventricular microvessels decreased as a function of age such that in the fetus it was 2.5-fold greater than in juvenile pigs. 15-F_2t-IsoP evoked more thromboxane formation in the fetus than in the newborn, which was greater than that in the juvenile periventricular region; this was associated with immunoreactive thromboxane A₂ (TXA₂) synthase expression in the fetus that was greater than that in newborn pigs, which was greater than that in juvenile pigs. 15-F_2t-IsoP–induced vasoconstriction was markedly inhibited by TXA₂ synthase and receptor blockers (CGS12970 and L670596). Vasoconstrictor effects of the TXA₂ mimetic U46619 on fetal, neonatal, and juvenile periventricular microvessels did not differ. 15-F_2t-IsoP increased TXA₂ synthesis by activating Ca²⁺ influx through non–voltage-gated channels in endothelial cells (SK&F96365 sensitive) and N-type voltage-gated channels (-conotoxin sensitive) in astrocytes; smooth muscle cells were not responsive to 15-F_2t-IsoP but generated Ca²⁺ transients to U46619 via L-type voltage-sensitive channels.

Conclusions—15-F_2t-IsoP causes periventricular brain region vasoconstriction in the fetus that is greater than that in the newborn, which in turn is greater than that in the juvenile due to greater TXA₂ formation generated through distinct stimulatory pathways, including from endothelial and astroglial cells. The resulting hemodynamic compromise may contribute to the increased vulnerability of the periventricular brain areas to oxidant stress–induced injury in immature subjects.

Editorial Comment

Earl F. Ellis, PhD, Guest Editor

Department of Pharmacology/Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond, Virginia

This article has been cited by other articles:

				S. Brault, F. Gobeil Jr., A. Fortier, J.-C. Honore, J.-S. Joyal, P. S. Sapieha, A. Kooli, E. Martin, P. Hardy, A. Ribeiro-da-Silva, et al. Lysophosphatidic acid induces endothelial cell death by modulating the redox environment Am J Physiol Regulatory Integrative Comp Physiol, March 1, 2007; 292(3): R1174 - R1183. [Abstract] [Full Text] [PDF]

				F. M. Faraci Reactive oxygen species: influence on cerebral vascular tone J Appl Physiol, February 1, 2006; 100(2): 739 - 743. [Abstract] [Full Text] [PDF]

				P. Pladys, F. Sennlaub, S. Brault, D. Checchin, I. Lahaie, N. L. O. Le, K. Bibeau, G. Cambonie, D. Abran, M. Brochu, et al. Microvascular rarefaction and decreased angiogenesis in rats with fetal programming of hypertension associated with exposure to a low-protein diet in utero Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1580 - R1588. [Abstract] [Full Text] [PDF]

				R. J. Gonzales, A. A. Ghaffari, S. P. Duckles, and D. N. Krause Testosterone treatment increases thromboxane function in rat cerebral arteries Am J Physiol Heart Circ Physiol, August 1, 2005; 289(2): H578 - H585. [Abstract] [Full Text] [PDF]

				P. MONTUSCHI, P. J. BARNES, and L. J. ROBERTS II Isoprostanes: markers and mediators of oxidative stress FASEB J, December 1, 2004; 18(15): 1791 - 1800. [Abstract] [Full Text] [PDF]

				J.-L. Cracowski and O. Ormezzano Isoprostanes, emerging biomarkers and potential mediators in cardiovascular diseases Eur. Heart J., October 1, 2004; 25(19): 1675 - 1678. [Full Text] [PDF]

				J. Belik, R. P. Jankov, J. Pan, M. Yi, C. R. Pace-Asciak, and A. K. Tanswell Effect of 8-isoprostaglandin F2{alpha} on the newborn rat pulmonary arterial muscle and endothelium J Appl Physiol, November 1, 2003; 95(5): 1979 - 1985. [Abstract] [Full Text] [PDF]

				F. Sennlaub, F. Valamanesh, A. Vazquez-Tello, A.M. El-Asrar, D. Checchin, S. Brault, F. Gobeil, M.H. Beauchamp, B. Mwaikambo, Y. Courtois, et al. Cyclooxygenase-2 in Human and Experimental Ischemic Proliferative Retinopathy Circulation, July 15, 2003; 108(2): 198 - 204. [Abstract] [Full Text] [PDF]

				J. Ou, Z. Ou, D. W. Jones, S. Holzhauer, O. A. Hatoum, A. W. Ackerman, D. W. Weihrauch, D. D. Gutterman, K. Guice, K. T. Oldham, et al. L-4F, an Apolipoprotein A-1 Mimetic, Dramatically Improves Vasodilation in Hypercholesterolemia and Sickle Cell Disease Circulation, May 13, 2003; 107(18): 2337 - 2341. [Abstract] [Full Text] [PDF]

				X. Hou, F. Gobeil Jr., A. M. Marrache, C. Quiniou, S. Brault, D. Checchin, S. G. Bernier, F. Sennlaub, J.-S. Joyal, D. Abran, et al. Increased platelet-activating factor-induced periventricular brain microvascular constriction associated with immaturity Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R928 - R935. [Abstract] [Full Text] [PDF]

				S. Brault, A. K. Martinez-Bermudez, A. M. Marrache, F. Gobeil Jr, X. Hou, M. Beauchamp, C. Quiniou, G. Almazan, C. Lachance, J. Roberts II, et al. Selective Neuromicrovascular Endothelial Cell Death by 8-Iso-Prostaglandin F2{alpha}: Possible Role in Ischemic Brain Injury Stroke, March 1, 2003; 34(3): 776 - 782. [Abstract] [Full Text] [PDF]

				M. H. Beauchamp, A. M. Marrache, X. Hou, F. Gobeil Jr, S. G. Bernier, P. Lachapelle, D. Abran, C. Quiniou, S. Brault, K. G. Peri, et al. Platelet-Activating Factor in Vasoobliteration of Oxygen-Induced Retinopathy Invest. Ophthalmol. Vis. Sci., October 1, 2002; 43(10): 3327 - 3337. [Abstract] [Full Text] [PDF]

				R. P. Jankov, R. Belcastro, E. Ovcina, J. Lee, H. Massaeli, S. J. Lye, and A. K. Tanswell Thromboxane A2 Receptors Mediate Pulmonary Hypertension in 60% Oxygen-exposed Newborn Rats by a Cyclooxygenase-independent Mechanism Am. J. Respir. Crit. Care Med., July 15, 2002; 166(2): 208 - 214. [Abstract] [Full Text] [PDF]

				L. J. Janssen and T. Tazzeo Involvement of TP and EP3 Receptors in Vasoconstrictor Responses to Isoprostanes in Pulmonary Vasculature J. Pharmacol. Exp. Ther., June 1, 2002; 301(3): 1060 - 1066. [Abstract] [Full Text] [PDF]

				D. H. Wright, D. Abran, M. Bhattacharya, X. Hou, S. G. Bernier, A. Bouayad, J.-C. Fouron, A. Vazquez-Tello, M. H. Beauchamp, R. I. Clyman, et al. Prostanoid receptors: ontogeny and implications in vascular physiology Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2001; 281(5): R1343 - R1360. [Abstract] [Full Text] [PDF]

				X. Hou, L. J. Roberts II, D. F. Taber, J. D. Morrow, K. Kanai, F. Gobeil Jr., M. H. Beauchamp, S. G. Bernier, G. Lepage, D. R. Varma, et al. 2,3-Dinor-5,6-dihydro-15-F2t-isoprostane: a bioactive prostanoid metabolite Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2001; 281(2): R391 - R400. [Abstract] [Full Text] [PDF]

				M. H. Beauchamp, A. K. Martinez-Bermudez, F. Gobeil Jr., A. M. Marrache, X. Hou, G. Speranza, D. Abran, C. Quiniou, P. Lachapelle, J. Roberts II, et al. Role of thromboxane in retinal microvascular degeneration in oxygen-induced retinopathy J Appl Physiol, June 1, 2001; 90(6): 2279 - 2288. [Abstract] [Full Text] [PDF]

				L. J. Janssen Isoprostanes: an overview and putative roles in pulmonary pathophysiology Am J Physiol Lung Cell Mol Physiol, June 1, 2001; 280(6): L1067 - L1082. [Abstract] [Full Text] [PDF]

				A. Mezzetti, F. Cipollone, and F. Cuccurullo Oxidative stress and cardiovascular complications in diabetes: isoprostanes as new markers on an old paradigm Cardiovasc Res, August 18, 2000; 47(3): 475 - 488. [Abstract] [Full Text] [PDF]

				P. Hardy, I. Dumont, M. Bhattacharya, X. Hou, P. Lachapelle, D. R. Varma, and S. Chemtob Oxidants, nitric oxide and prostanoids in the developing ocular vasculature: a basis for ischemic retinopathy Cardiovasc Res, August 18, 2000; 47(3): 489 - 509. [Abstract] [Full Text] [PDF]