[Frontiers in Bioscience E2, 369-379, January 1, 2010]

Age-related changes in isoprostane-mediated relaxation of piglet blood vessels

Gema Gonzalez-Luis1, Francisco Perez-Vizcaino2,. Carlos E. Blanco3, Eduardo Villamor3

1Division of Neonatology, Department of Pediatrics, Hospital Universitario Materno-Infantil de Canarias, 35016 Las Palmas de Gran Canaria, Spain, 2Department of Pharmacology, School of Medicine, Complutense University, CIBER Enfermedades Respiratorias (Ciberes), 28040 Madrid, Spain, 3Department of Pediatrics, Maastricht University Medical Center (MUMC+), School for Oncology and Developmental Biology (GROW), 6202 AZ Maastricht, the Netherlands

TABLE OF CONTENTS

1. Abstract
2. Introduction
2. Introduction
3. Materials and methods
3.1. Tissue preparation
3.2. Isometric force measurement
3.3. Drugs and solutions
3.4. Analysis of data
4. Results
5. Discussion
6. Acknowledgments
7. References

1. ABSTRACT

We studied the putative relaxant effects of several isoprostanes (8-iso-PGE1, and 8-iso-PGE2, 8-iso-PGF1alpha, 8-iso-PGF1beta, 8-iso-PGF2alpha, and 8-iso-PGF2beta) on pulmonary (PA), mesenteric (MA), coronary (CA) arteries and pulmonary veins (PV), from newborn and 2-week-old piglets. Isoprostanes were compared with agonists of the EP (PGE1, PGE2, and misoprostol), DP (PGD2), and IP (iloprost) receptors. Isoprostane-induced relaxation was only observed when TP receptors were occupied (by U46619) or blocked (by SQ 29,548). Under these conditions, 8-iso-PGE2 induced a relaxation of PA (but not PV or MA) that increased with postnatal age. 8-iso-PGE1, 8-iso-PGE2, and 8-iso-PGF2alpha evoked modest relaxations in CA. 8-iso-PGE2-induced relaxation of PA was impaired by endothelium removal and by the presence of blockers of NO synthase (L-NAME), guanylate cyclase (ODQ), or EP receptor (AH6809). PGE1, PGE2, and misoprostol (but not PGD2 or iloprost) induced a relaxation of PA that increased with age. In conclusion, occupancy or blockade of TP receptors unmasked a relaxant effect of 8-iso-PGE2 in piglet PA. This relaxation increased with postnatal age, was endothelium-dependent and involved EP receptors and NO.