EFFECT OF CYCLOSPORINE-A INJECTION ON PER IPHERAL VENOUS RESISTANCE IN DOGS

We have studied the effect of cyclosporin on the peripheral venous sys tem. CSA was injected into an isolated hind limb saphenous vein perfus ed at constant flow in 29 dogs. Reactivity of the vein was tested with infusions of norepinephrine (NE) before and after CSA. In a 1(st) gro up of 7 dogs, CSA at doses of 5, 10 and 20 mg was infused over a 1O-mi nute period. In a 2(nd) group of 8 dogs, 20 mg of CSA was infused over 20 minutes and, injections of 6, 12 and 24 mu g of NE were administer ed before and during CSA. In a 3(rd) (n = 7) and 4(th) (n = 7) groups of animals, 30mg of CSA was injected over 60 minutes and injections of 3, 6, 12 mu g of NE were given before and during CSA. In the last gro up, an ipsilateral lumbar sympathectomy was performed before CSA injec tion. The infusion of CSA over periods of 10 and 20 minutes did not ca use significant changes in venous perfusion pressure. The infusion of 30 mg of CSA over 60 minutes caused an increase in venous perfusion pr essure from 44 +/- 2 mm Hg to 58 +/- 5 mm Hg (p < 0.0001). Surgical sy mpathectomy prevented the venoconstrictor response to CSA. Injections of 3, 6 and 12 +/- of NE caused averaged increases of 25 +/- 6, 39 +/- 9 and 53 +/- 10 mm Hg before CSA, and of 45 +/- 7, 69 +/- 12 and 84 /- 8 mm Hg respectively after CSA injections, a significant increase ( p = 0.03). In conclusion, CSA causes a vasoconstriction of the sapheno us vein through stimulation of the sympathetic nervous system and pote ntiates the venoconstrictor effect of NE.