Endothelium-dependent contractions are associated with both augmented expression of prostaglandin H synthase-1 and hypersensitivity to prostaglandin H2 in the SHR aorta

Circ Res. 1995 Jun;76(6):1003-10. doi: 10.1161/01.res.76.6.1003.

Abstract

Prostaglandin H2 (PGH2 [endoperoxide]) is an immediate product of prostaglandin H (PGH) synthase activity (cyclooxygenase) and a likely candidate to mediate endothelium-dependent contractions evoked by acetylcholine in the aorta of the spontaneously hypertensive rat (SHR). Experiments were designed to investigate whether or not endothelium-dependent contractions were associated with an increased expression of PGH synthase, an augmented acetylcholine-induced release of PGH2, and/or a hypersensitivity of the smooth muscle to endoperoxides in SHR aorta compared with normotensive Wistar-Kyoto (WKY) aorta. In SHR aorta, endothelium-dependent contractions to acetylcholine were abolished by tenidap (10(-8) mol/L), a preferential PGH synthase-1 inhibitor, but slightly impaired by NS-398 (10(-6) mol/L), a preferential PGH synthase-2 inhibitor. PGH synthase-1 expression, which was evaluated by both reverse transcriptase-polymerase chain reaction and Western blotting, was about twofold greater in preparations with endothelium from SHR than from WKY rats. There was no difference in PGH synthase-1 expression between preparations with and those without endothelium in both strains. In SHR but not WKY aortas, acetylcholine (10(-5) mol/L, 5 minutes) caused a significant endothelium-dependent release of PGH2 as measured by gas chromatography/mass spectrometry. PGH2 evoked more potent contractions in rings without endothelium from SHR than from WKY rats, whereas the thromboxane analogue U46619 and prostaglandin F2 alpha caused a comparable response in both preparations. These results show that endothelium-dependent contractions to acetylcholine in SHR aorta are associated with a greater expression of PGH synthase-1, a significant release of PGH2, and a hypersensitivity of the smooth muscle to the endoperoxide.

Publication types

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

MeSH terms

  • Acetylcholine / pharmacology
  • Analysis of Variance
  • Animals
  • Aorta / drug effects
  • Aorta / immunology
  • Aorta / physiology*
  • Autoradiography
  • Blotting, Western
  • Endothelium, Vascular / physiology*
  • Gene Amplification*
  • Hypersensitivity*
  • Male
  • Muscle Contraction*
  • Muscle, Smooth, Vascular / immunology
  • Muscle, Smooth, Vascular / physiology
  • Polymerase Chain Reaction
  • Prostaglandin H2
  • Prostaglandin-Endoperoxide Synthases / analysis
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandins H / analysis
  • Prostaglandins H / immunology*
  • RNA, Messenger / genetics
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred WKY
  • Transcription, Genetic*

Substances

  • Prostaglandins H
  • RNA, Messenger
  • Prostaglandin H2
  • Prostaglandin-Endoperoxide Synthases
  • Acetylcholine