Long-term portal hypertension increases the vasodilator response to acetylcholine in rat aorta: role of prostaglandin I₂

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, TXB₂ (thromboxane B₂) and 6-keto PGF_1α (prostaglandin F_1α) 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.