title: Orchidectomy increases the formation of prostanoids and modulates their role in the acetylcholine-induced relaxation in the rat aorta.
abstract: OBJECTIVE
  This study examines the effect of endogenous male sex hormones on thromboxane A2 (TXA2), prostaglandin (PG) I2, PGF(2 alpha), and PGE I2 release, as well as their role in acetylcholine (ACh)-mediated relaxation in the aorta.
  
  
  RESULTS
  Aortic segments from orchidectomized and control male Sprague-Dawley rats were used to measure COX-2 protein expression. ACh-induced relaxation of these segments was also determined in the absence and presence of the COX-2 inhibitor NS-398, the TXA2 synthesis inhibitor furegrelate, the PGI2 synthesis inhibitor tranylcypromine (TCP), or the thromboxane-prostanoid (TP) receptor antagonist SQ-29 548. Furthermore, TXA2, PGI2, PGF(2 alpha), and PGE2 release as well as the vasomotor effect of exogenous TXA2, PGI2, PGF(2 alpha), and PGE2 were measured. COX-2 expression was increased in aortas from orchidectomized rats. NS-398 did not modify the ACh-induced relaxation in arteries from both control or orchidectomized rats. Furegrelate did not modify the ACh-induced relaxation in aortas from control animals but, in aortas from orchidectomized rats, it increased that response. TCP decreased the ACh-induced relaxation in both groups. The TP receptor antagonist, SQ29 548 failed to modify ACh-induced relaxation in aortas from either rat group. Pre-incubating arteries from orchidectomized rats with TCP plus furegrelate did not modify the decrease in the ACh response induced by TCP alone, but this response was restored by co-incubation of TCP plus SQ29 548. ACh-induced TXA2, PGI2, PGF(2 alpha), and PGE2 release were increased by orchidectomy. The presence of furegrelate plus TCP increased the ACh-induced PGE2 release more in arteries from orchidectomized than in those from control rats. The contractile responses induced by the TXA2 mimetic U-46619 or by exogenous PGF(2 alpha) were similar in arteries from control and orchidectomized rats, while those induced by exogenous PGE2 were increased in arteries from orchidectomized rats; the vasodilator response induced by exogenous PGI2 was decreased in arteries from orchidectomized rats.
  
  
  CONCLUSIONS
  These data show that endogenous male sex hormone deprivation increases COX-2 expression, the release of TXA2, PGI2, PGF(2 alpha), and PGE2 and the contractile response induced by exogenous PGE2 and TXA2, while it decreases the relaxation induced by exogenous PGI2. Despite the predominance of vasoconstrictor prostanoids derived from COX-2 in aortas from orchidectomized rats, the ACh-induced relaxation remains increased.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo 4, 28029 Madrid, Spain.
authors.forename: Aina
authors.initials: A
authors.lastname: Martorell
authors.forename: Javier
authors.initials: J
authors.lastname: Blanco-Rivero
authors.forename: Rosa
authors.initials: R
authors.lastname: Aras-López
authors.forename: Ana
authors.initials: A
authors.lastname: Sagredo
authors.forename: Gloria
authors.initials: G
authors.lastname: Balfagón
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ferrer
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D001794:Blood Pressure; D019086:Bridged Bicyclo Compounds, Heterocyclic; D051546:Cyclooxygenase 2 / Q000502:physiology; D011464:Epoprostenol / Q000502:physiology; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D009919:Orchiectomy; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000097:blood / Q000502:physiology*; D013928:Thromboxane A2 / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011453:Prostaglandins; D013739:Testosterone; D013928:Thromboxane A2; C045749:SQ 29548; D011464:Epoprostenol; D051546:Cyclooxygenase 2; D000109:Acetylcholine