title: Aging and prostacyclin responses in aorta and platelets from WKY and SHR rats.
abstract: In spontaneously hypertensive rat (SHR) aorta, prostacyclin is an endothelium-derived contracting factor contributing to the endothelial dysfunction. This study was designed to determine whether the impairment of the prostacyclin response is influenced by aging and whether such a dysfunction is observed in platelets. Isometric tension was measured in aortic rings, and aggregation was studied in platelet-rich plasma taken from 3-, 6-, and 15-mo-old Wistar-Kyoto rats (WKY) and SHR. In aorta from 3- and 6-mo-old WKY, prostacyclin and beraprost [prostacyclin receptor (IP) agonists] produced relaxations that were enhanced by Triplion (thromboxane-prostanoid receptor antagonist). In 15-mo-old WKY, the relaxations to beraprost were maintained, but not those to prostacyclin. In SHR aorta, prostacyclin or beraprost produced no or minor relaxations, which, in younger SHR, were enhanced by Triplion. In both strains, the relaxations were inhibited by CAY-10441 (IP receptor antagonist). The relaxations to forskolin and isoproterenol were reduced with aging. When compared with those of WKY, the relaxations to isoproterenol were reduced in 3- but not in 6- or 15-mo-old SHR, whereas those to forskolin were consistently diminished at any given age. Whatever the age, prostacyclin and beraprost produced CAY-10441-sensitive inhibitions of ADP-induced platelet aggregation. Both agonists were more potent in SHR than in WKY. Therefore, in platelets from WKY and SHR, the IP receptor-dependent antiaggregant response is functional and maintained during aging. In aorta from WKY those responses are reduced by aging and, in SHR, are already compromised at 3 mo. This dysfunction of the IP receptor is only partially explained by a general dysfunction of the adenylate cyclase pathway.
authors.affiliation: Départment d'Angiologie, Institut de Recherches Servier, 11 rue des Moulineaux 92150 Suresnes, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Gomez
authors.forename: Cédric
authors.initials: C
authors.lastname: Schwendemann
authors.forename: Séverine
authors.initials: S
authors.lastname: Roger
authors.forename: Serge
authors.initials: S
authors.lastname: Simonet
authors.forename: Jerôme
authors.initials: J
authors.lastname: Paysant
authors.forename: Christine
authors.initials: C
authors.lastname: Courchay
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Verbeuren
authors.forename: Michel
authors.initials: M
authors.lastname: Félétou
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000375:Aging / Q000097:blood / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D044062:Prostaglandins I / Q000097:blood / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044006:Receptors, Epoprostenol / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism; D017482:Receptors, Thromboxane / Q000378:metabolism; D015398:Signal Transduction; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D010975:Platelet Aggregation Inhibitors; D044062:Prostaglandins I; C491909:Ptgir protein, rat; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D014665:Vasodilator Agents; D000262:Adenylyl Cyclases