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

Front Biosci (Elite Ed). 2010 Jan 1;2:369-79. doi: 10.2741/e97.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age Factors
  • Analysis of Variance
  • Animals
  • Coronary Vessels / drug effects
  • Guanylate Cyclase / metabolism
  • Isoprostanes / pharmacology*
  • Mesenteric Arteries / drug effects
  • NG-Nitroarginine Methyl Ester / metabolism
  • Nitric Oxide Synthase / antagonists & inhibitors
  • Pulmonary Artery / drug effects
  • Pulmonary Veins / drug effects
  • Sus scrofa
  • Vasodilation / drug effects*
  • Xanthones / metabolism

Substances

  • Isoprostanes
  • Xanthones
  • 6-isopropoxy-9-oxoxanthene-2-carboxylic acid
  • Nitric Oxide Synthase
  • Guanylate Cyclase
  • NG-Nitroarginine Methyl Ester