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Atherosclerosis-related remodeling of aortic relaxation to purines in the Watanabe heritable hyperlipidemic rabbit.

Abstract
The mechanism of the unimpaired relaxant effect of ATP in the Watanabe heritable hyperlipidemic rabbit aorta was investigated to elucidate the involvement of P2y purinoceptor at the endothelial level during atherosclerosis. Experiments were carried out on isolated thoracic aorta from such rabbits that were 12 months of age. The potent P2y purinoceptor agonist, 2-methylthio-ATP, did not induce any endothelium- or smooth muscle-dependent relaxation, thus excluding any involvement by the P2y purinoceptor. ADP, but not AMP, produced relaxation of the aorta by acting at both endothelial and smooth muscle levels. Adenosine relaxed the vessel by acting only in smooth muscle. The maintained endothelial relaxant effect of ATP and ADP is therefore not due to activation of P1 or P2y purinoceptors but may involve activation of a remodeled purinergic receptor site that emerges with the progression of atherosclerosis. This site is antagonized by methylene blue. The disorganization of the endothelial monolayer observed in the morphological analysis may be related to functional remodeling of the endothelial purinergic activity in atherosclerosis.
AuthorsE Ragazzi, A Chinellato, L Pandolfo, G Froldi, L Caparrotta, M Prosdocimi, G Aliev, G Fassina
JournalThe Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 266 Issue 2 Pg. 1091-6 (Aug 1993) ISSN: 0022-3565 [Print] United States
PMID8355183 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Adenine Nucleotides
  • Receptors, Purinergic
  • Adenosine Diphosphate
  • Adenosine Triphosphate
  • Methylene Blue
Topics
  • Adenine Nucleotides (pharmacology)
  • Adenosine Diphosphate (pharmacology)
  • Adenosine Triphosphate (pharmacology)
  • Animals
  • Aorta, Thoracic (drug effects, physiology, ultrastructure)
  • Arteriosclerosis (genetics, physiopathology)
  • Endothelium, Vascular (physiology)
  • Female
  • Male
  • Methylene Blue (pharmacology)
  • Microscopy, Electron
  • Rabbits
  • Receptors, Purinergic (physiology)
  • Vasodilation (drug effects)

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