title: Endothelial nucleotide-mediated aorta relaxation in aged Watanabe heritable hyperlipidemic rabbits.
abstract: We investigated the activity of muscarinic and purinergic endothelial receptors during atherosclerosis in Watanabe heritable hyperlipidemic (WHHL) rabbit aorta. Experiments were performed on isolated thoracic aorta from WHHL rabbits aged 1 and 2.5 years. The relaxant response to acetylcholine (ACh) was progressively reduced with aging, being almost completely abolished in 2.5-year-old rabbits. The relaxant effect of ATP was not affected by the P2-purinoceptor antagonist suramin, thus excluding any involvement of relaxant P2y purinoceptors in both considered ages. The pyrimidine UTP, acting on nucleotide (P2U) receptors, produced concentration-dependent relaxation in 1-year-old WHHL rabbit aorta only in the presence of endothelium; relaxation was reduced in older animals. In 1-year-old WHHL rabbits, the endothelium-dependent relaxant effect of UTP was not antagonized by suramin, but was by the inhibitors of nitric oxide (NO) effect, methylene blue (MB) and L-NG-nitroarginine methyl ester (L-NAME), suggesting involvement of NO in the UTP-mediated relaxation. Morphological data from electron microscopy observations indicated the presence of typical atherosclerotic lesions and extensive dystrophic changes in endothelial cells, gradually evolving at 1 and 2.5 years of age. The present data suggest that progressive atherosclerosis differentially affects the activity of endothelial receptors: The most precociously altered is the P2y-purinoceptor, followed by an impairment of the muscarinic and finally of the P2U-purinoceptor.
authors.affiliation: Department of Pharmacology, University of Padova, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ragazzi
authors.forename: A
authors.initials: A
authors.lastname: Chinellato
authors.forename: L
authors.initials: L
authors.lastname: Pandolfo
authors.forename: G
authors.initials: G
authors.lastname: Froldi
authors.forename: L
authors.initials: L
authors.lastname: Caparrotta
authors.forename: G
authors.initials: G
authors.lastname: Aliev
authors.forename: M
authors.initials: M
authors.lastname: Prosdocimi
authors.forename: G
authors.initials: G
authors.lastname: Fassina
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000375:Aging / Q000502:physiology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001161:Arteriosclerosis / Q000473:pathology / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology* / Q000648:ultrastructure; D005260:Female; D006950:Hyperlipidemia, Familial Combined / Q000503:physiopathology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D058914:Purinergic Antagonists; D011817:Rabbits; D011976:Receptors, Muscarinic / Q000502:physiology*; D011983:Receptors, Purinergic / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D014544:Uridine Triphosphate / Q000494:pharmacology
chemical_list: D018727:Muscarinic Antagonists; D058914:Purinergic Antagonists; D011976:Receptors, Muscarinic; D011983:Receptors, Purinergic; D009569:Nitric Oxide; D013498:Suramin; D000255:Adenosine Triphosphate; D001120:Arginine; D000109:Acetylcholine; D008751:Methylene Blue; D014544:Uridine Triphosphate; D019331:NG-Nitroarginine Methyl Ester