Involvement of cyclo-oxygenase-1-mediated prostacyclin synthesis in the vasoconstrictor activity evoked by ACh in mouse arteries

This study was to determine whether the endothelium of mouse major arteries produces prostacyclin (PGI2) and, if so, to determine how PGI2 affects vasomotor reactivity and whether cyclo-oxygenase-1 (COX-1) contributes to PGI2 synthesis. Abdominal aortas, carotid and femoral arteries were isolated from wild-type mice and/or those with COX-1 or -2 deficiency (COX-1-/-; COX-2-/-) for biochemical and/or functional analyses. The PGI2 metabolite 6-keto-PGF1a was analysed with high-performance liquid chromatographymass spectroscopy, while vasoreactivity was determined with isometric force measurement. Results showed that in the abdominal aorta, ACh evoked endothelium-dependent production of 6-keto-PGF1a, which was abolished by COX-1-/-, but not by COX-2-/-. Interestingly, COX-1-/- enhanced the dilatation in response to ACh, while PGI2, which evoked relaxation of the mesenteric artery, caused contraction that was abolished by antagonizing thromboxane prostanoid (TP) receptors in the abdominal aorta. However, the TP receptor agonist U46619 evoked similar contractions in the abdominal aorta and mesenteric artery. Also, antagonizing TP receptors enhanced the relaxation in response to PGI2 in mesenteric arteries. Real-time PCR showed that the PGI2 (IP) receptor mRNA level was lower in the abdominal aorta than in mesenteric arteries. In addition, COX-1-/- not only abolished the contraction in response to ACh following NO inhibition in abdominal aorta, but also those in the carotid and femoral arteries. These results demonstrate an explicit role for endothelial COX-1 in PGI2 synthesis and suggest that in given mouse arteries, PGI2 mediates not dilatation but rather vasoconstrictor activity, possibly due to a low expression or functional presence of IP receptors, which enables PGI2 to act mainly on TP receptors.