CYCLOSPORINE IMPAIRS VASODILATION WITHOUT INCREASED SYMPATHETIC ACTIVITY IN HUMANS

Hypertension and nephrotoxicity frequently complicate treatment with c yclosporine; two suggested mechanisms are increased sympathetic activi ty and altered vascular reactivity. It is difficult to assess these me chanisms in patients receiving cyclosporine after transplantation beca use of the accompanying major physiological alterations. Therefore, we studied 12 patients with rheumatoid arthritis twice-while they were t aking and not taking cyclosporine. We measured vascular response in th e dorsal hand vein using the linear variable differential transformer technique. Cyclosporine treatment significantly attenuated vasodilatio n induced by 60 ng/min isoproterenol (no cyclosporine, 19.8+/-3.5% ver sus cyclosporine, 7.9+/-2.2%; P=.02) and prostaglandin E(1), al 1000 p g/min (no cyclosporine, 72.6+/-10.2% versus cyclosporine. 45.6+/-9.0%) and 2000 pg/min (no cyclosporine, 100.8+/-14.7% Versus cyclosporine, 68.6+/-8.0%; F=5.47, P=.047). However, neither vascular response to ph enylephrine or nitroglycerin nor sympathetic activity assessed by meas urement of norepinephrine spillover with a radioisotope dilution techn ique was affected by cyclosporine (no cyclosporine, 516.1+/-47.9 ng/mi n versus cyclosporine, 476.6+/-51.8 ng/min; P=.42). Cyclosporine impai red venodilation in response to two agonists that act through adenylat e cyclase without altering alpha-agonist-induced venoconstriction or s ympathetic activity. Therefore, in humans impaired vasodilation rather than sympathetic activation or enhanced vasoconstriction may be an im portant mechanism for the alterations of vascular lone that occur afte r long-term cyclosporine administration.