title: Long-term portal hypertension increases the vasodilator response to acetylcholine in rat aorta: role of prostaglandin I2.
abstract: In the present study, we have analysed both the effect of long-term portal hypertension on the vasomotor response to acetylcholine in rat aorta and the mechanism involved in this response. For this purpose, sham-operated rats and rats with pre-hepatic PH (portal hypertension; triple partial portal vein ligation) were used at 21 months after surgery. The participation of NO and COX (cyclo-oxygenase) derivatives in the vasodilator response elicited by acetylcholine after incubation with L-NAME (NG-nitro-L-arginine methyl ester), indomethacin, SC-560, NS-398, tranylcypromine and furegrelate, was analysed. NO, TXB2 (thromboxane B2) and 6-keto PGF1alpha (prostaglandin F1alpha) release were measured. In addition, SNP (sodium nitroprusside), U-46619, PGI2 and forskolin vasomotor responses were analysed. COX-1 and COX-2 expression was also determined. The acetylcholine-induced vasodilating response was higher in rats with PH. TXA2 and NO release, and SNP and U-46619 sensitivity were similar in both groups. PGI2 release was not modified by portal hypertension, but vasodilator responses to this prostanoid and to forskolin were higher in rats with PH. COX-1 and COX-2 expression remained unmodified by surgery. In conclusion, increased vasodilation to acetylcholine is maintained in long-term PH. Although the participation of endothelial NO remained unmodified, the COX-2 derivative PGI2 does participate through an increased vasodilator response.
authors.affiliation: Departamento de Fisiología, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain.
authors.forename: Javier
authors.initials: J
authors.lastname: Blanco-Rivero
authors.forename: Ma Angeles
authors.initials: MA
authors.lastname: Aller
authors.forename: Jaime
authors.initials: J
authors.lastname: Arias
authors.forename: Mercedes
authors.initials: M
authors.lastname: Ferrer
authors.forename: Gloria
authors.initials: G
authors.lastname: Balfagón