Gene expression changes of prostanoid synthases in endothelial cells and prostanoid receptors in vascular smooth muscle cells caused by aging and hypertension

Physiol Genomics. 2008 Feb 19;32(3):409-18. doi: 10.1152/physiolgenomics.00136.2007. Epub 2007 Dec 4.

Abstract

The present study was designed to assess whether or not changes in genomic expression of cyclooxygenases (COX-1, COX-2), endothelial nitric oxide synthase (eNOS), and prostanoid synthases in the endothelium and of prostanoid receptors in vascular smooth muscle contribute to the occurrence of endothelium-dependent contractions during aging and hypertension. Gene expression was quantified by real-time PCR using isolated endothelial cells and smooth muscle cells (SMC) from the aorta of Wistar-Kyoto and spontaneously hypertensive rats. Genes for all known prostanoid synthases and receptors were present in endothelial cells and SMC, respectively. Aging caused overexpression of eNOS, COX-1, COX-2, thromboxane synthase, hematopoietic-type prostaglandin D synthase, membrane prostaglandin E synthase-2, and prostaglandin F synthase in endothelial cells and COX-1 and prostaglandin E(2) (EP)(4) receptors in SMC. Hypertension augmented the expression of COX-1, prostacyclin synthase, thromboxane synthase, and hematopoietic-type prostaglandin D synthase in endothelial cells and prostaglandin D(2) (DP), EP(3), and EP(4) receptors in SMC. The increase in genomic expression of endothelial COX-1 explains why in aging and hypertension the endothelium has greater propensity to release cyclooxygenase-derived vasoconstrictive prostanoids. The expression of prostacyclin synthase was by far the most abundant, explaining why the majority of the COX-1-derived endoperoxides are transformed into prostacyclin, substantiating the role of prostacyclin as an endothelium-derived contracting factor. The expression of thromboxane synthase was increased in the cells of aging or hypertensive rats, explaining why the prostanoid can contribute to endothelium-dependent contractions. It is uncertain whether the gene modifications caused by aging and hypertension directly contribute to endothelium-dependent contractions or rather to vascular aging and the vascular complications of the hypertensive process.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylcholine / pharmacology
  • Aging / genetics*
  • Animals
  • Aorta, Thoracic / drug effects
  • Cyclooxygenase 1 / biosynthesis
  • Cyclooxygenase 1 / genetics
  • Endothelial Cells / metabolism*
  • Enzyme Induction
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Hypertension / genetics*
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / genetics
  • Muscle Proteins / biosynthesis*
  • Muscle Proteins / genetics
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / pathology
  • Myocytes, Smooth Muscle / metabolism*
  • Nitric Oxide Synthase Type II / biosynthesis
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type III
  • Phenylephrine / pharmacology
  • Prostaglandin-Endoperoxide Synthases / biosynthesis*
  • Prostaglandin-Endoperoxide Synthases / genetics
  • Prostaglandins / biosynthesis
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Receptors, Prostaglandin / biosynthesis*
  • Receptors, Prostaglandin / genetics

Substances

  • Membrane Proteins
  • Muscle Proteins
  • Prostaglandins
  • Receptors, Prostaglandin
  • Phenylephrine
  • Nitric Oxide Synthase Type II
  • Nitric Oxide Synthase Type III
  • Nos3 protein, rat
  • Cyclooxygenase 1
  • Prostaglandin-Endoperoxide Synthases
  • Ptgs1 protein, rat
  • Acetylcholine