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 endothelium dependent and endothelium independent vasoconstriction and vasodilatation of rat mesenteric arteries were studied in comparison with cyclosporin (CyA). Four groups of male Sprague-Dawley rats were treated with CyA (5 mg/kg/day, 20 mg/kg/day or solvent orally) or FK 506 (1.5 mg/kg/day, 3 mg/kg/day, intraperitoneal injection), respectively, for 14 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 endothelin-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 endothelin-1-induced vasoconstrictions were increased (p < 0.05) by cyclosporin (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 relaxation by nitroprusside. In contrast, FK 506 did not reduce the relaxation responses and, hence, may have potentially less hypertensiogenic effects than CyA.