Effects of indomethacin and prostaglandins I2 and E2 on the tone of human isolated mesenteric arteries

The actions of indomethacin (IND), PGE2 and PGI2 were studied on the tone of isolated mesenteric arteries obtained from operated patients. The cyclooxygenase inhibitors IND (3 mumol/l) and suprofen (0.58 mumol/l) increased the resting tone and potentiated the contractile responses to electrical stimulation and noradrenaline. Low concentrations of PGE2 (0.7-5.6 X 10(-9) mol/l) decreased the baseline tone and reduced the stimulation-evoked contractions whereas higher concentrations (from 5.7 X 10(-8) mol/l) increased the tone of vessels. PGI2 (0.7-10.8 X 10(-9) mol/l) also relaxed IND-treated arteries but, in contrast to PGE2, it did not produce contraction even at a concentration of 10(-6) mol/l. Prostacyclin reduced the tone evoked and sustained by a high concentration of PGE2 or PGF2 alpha, the IC50 values being 46.2 or 7.9 X 10(-9) mol/l, respectively. The contractile responses to electrical stimulation and to noradrenaline were also inhibited by PGI2 (IC50 5.6 and 6.8 X 10(-9) mol/l, respectively). These results suggest that the smooth muscle cells of human mesenteric arteries are just as sensitive to IND, PGE2 and PGI2 as are those from laboratory animals. Our observations may be of clinical importance.