FK-506 REDUCES THE ENDOTHELIUM-DEPENDENT RELAXATION OF RAT MESENTERIC-ARTERIES LESS-THAN CYCLOSPORINE

The effects of the new immunosuppressive agent FK 506 on both endothel ium dependent and endothelium independent vasoconstriction and vasodil atation of rat mesenteric arteries were studied in comparison with cyc losporin (CyA). Four groups of male Sprague-Dawley rats were treated w ith CyA (5 mg/kg/day, 20 mg/kg/day or solvent orally) or FK 506 (1.5 m g/kg/day, 3 mg/kg/day, intraperitoneal injection), respectively, for 1 4 days. Mesenteric arteries (200-250 mu m) were mounted on a myograph for isometric tension recording. The cumulative concentration-response curves to KCl, noradrenaline (NA), serotonin, vasopressin and endothe lin-l were recorded. The maximal relaxation of acetylcholine (10 mu M) and nitroprusside (100 mu M) were expressed as a percentage of the NA (10 mu M) induced contractions. The maximal vasopressin- and endothel in-1-induced vasoconstrictions were increased (p < 0.05) by cyclospori n (5 mg/kg/day) but not by FK 506 (1.5 mg/kg/day). Both dosages of CyA depressed endothelium dependent relaxations induced by acetylcholine (p < 0.05), the higher dose reduced also the endothelium-independent r elaxation by nitroprusside. In contrast, FK 506 did not reduce the rel axation responses and, hence, may have potentially less hypertensiogen ic effects than CyA.