Vasoconstrictor effect of cyclosporin on the mesenteric artery in the dog

To evaluate the effect of cyclosporin (CyA) on the mesenteric arterial bed, studies were performed on the isolated mesenteric artery perfused at a constant flow in 20 dogs. Changes in mesenteric perfusion pressure reflected variations in vascular resistance. Pure powder CyA was dissolved in autologous blood and injected at doses of 5, 10, 20 and 40 mg. Infusions of 5 and 10 mg CyA caused nonsignificant mean increases of 3 +/- 2 mm Hg [95% confidence interval (CI) -2 to +7; P > 0.05] and 3 +/- 3 mm Hg (95% CI -3 to +9; P > 0.05) in mesenteric perfusion pressure, with CyA blood levels in the mesenteric vein averaging 466 +/- 153 and 692 +/- 130 nmol/l, respectively, at the end of the injections. Infusions of 20 and 40 mg CyA caused significant increases in mesenteric perfusion pressure averaging 11 +/- 3 mm Hg (95% CI 3-18; P < 0.05) and 26 +/- 4 mm Hg (95% CI 16-34; P < 0.05), respectively. CyA blood levels at the end of infusion averaged 806 +/- 85 and 1118 +/- 89 nmol/l, respectively, in the mesenteric vein. Blockade of alpha-adrenergic receptors with phentolamine abolished the CyA vasoconstriction of the mesenteric artery, with the increase in perfusion pressure averaging 16 +/- 4 mm Hg before and 3 +/- 3 mm Hg after phentolamine (P < 0.05). Thus, in the dog, CyA causes an acute vasoconstriction of the mesenteric artery through stimulation of alpha-adrenergic receptors.