Effect of three loop diuretics and prostaglandins E2 & I2 on the isolated perfused rat mesenteric vasculature

Rat superior mesenteric vascular bed was isolated, perfused by the artery with Krebs solution and the perfusion pressure monitored. Dose-response curves to noradrenaline and KCl administered as bolus doses were obtained. A 1 hr continuous infusion of either piretanide (10 micrograms ml-1) frusemide (40 micrograms ml-1) or bumetanide (2 micrograms ml-1) decreased the sensitivity of the preparation to noradrenaline but not to KCl. This effect was antagonized by flurbiprofen (12 micrograms ml-1) pretreatment. A 1 hr continuous infusion of prostaglandin (PG)E2 increased the sensitivity of the preparation to both noradrenaline and KCl. PGI2 (5 ng bolus) or diuretic perfusion antagonized the responses to noradrenaline but not those to KCl. PGI2 and diuretics in combination further decreased the responsiveness of the preparation to noradrenaline. KCl responses were unaffected by either PGI2 or diuretics, alone or combined. The results suggest that the loop diuretics decrease the responsiveness of the isolated rat superior mesenteric vascular bed preparation to noradrenaline, possibly by increasing the level of PGI2, an effect which may be an important factor in the cardiovascular activity of the diuretics.