Long-term portal hypertension increases the vasodilator response to acetylcholine in rat aorta: role of prostaglandin I_2

摘要

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 (N~G-nitro-L-arginine methyl ester), indomethacin, SC-560, NS-398, tranylcypromine and furegrelate, was analysed. NO, TXB_2 (thromboxane B_2) and 6-keto PGF_(1alpha) (prostaglandin F_(1alpha)) 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. TXA_2 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 PGI_2 does participate through an increased vasodilator response.