Objective: Nonocclusive mesenteric ischemia (NOMI) is accompanied by mesenteric artery spasms that are at least in part due to endothelin system activation. Acute treatment includes intra-arterial infusion of vasodilators such as iloprost, prostaglandin E1 (PGE1), and papaverine. Their effectiveness is not well characterized in human mesenteric arteries. We directly compared their potency to relax isolated human mesenteric arteries. To explore the potential of Rock inhibition to treat mesenteric artery spasms, we tested if endothelin-1 (ET-1)-induced mesenteric artery constrictions depend on rho kinase (Rock).
Methods: Mesenteric artery segments were obtained from patients who underwent elective abdominal surgery. Vasodilator concentration-response curves were recorded from ET-1-preconstricted vessels by small vessel myography. Rock expression was investigated by Western blot and the potency of Rock inhibition to blunt ET-1-induced mesenteric artery constriction was tested.
Results: Iloprost, PGE1, and papaverine similarly reduced vascular tone to 20% to 30% of ET-1-induced wall tension. In human mesenteric arteries, logEC50 was significantly less for iloprost than for PGE1 or papaverine. Respective logEC50 values were -7.72 ± 0.08 mol/L, -6.58 ± 0.17 mol/L, and -6.73 ± 0.19 mol/L in 150 μm to 300 μm lumen diameter arteries. These vessels were also more sensitive to iloprost than 500 μm to 1,000 μm lumen diameter arteries (logEC50 -7.29 ± 0.07 mol/L). Rock1 and Rock2 were expressed in human mesenteric arteries but Rock inhibition did not significantly affect ET-1-induced vasoconstrictions.
Conclusions: Iloprost, PGE1, and papaverine have a similar potency to relax mesenteric arteries. Our data suggest that iloprost but not Rock inhibition may be particularly useful to treat ET-1-induced spasms of distal mesenteric arteries.