We postulate that the sympathoexcitatory response associated with the
immunosuppressive agent cyclosporin A is due to an upward resetting of
the arterial baroreflex. We performed studies in conscious intact and
sinoaortic-denervated rabbits instrumented with catheters and renal n
erve electrodes. In intact rabbits, cyclosporin A (20 mg/kg IV, 30 min
utes) produced significant increases in renal sympathetic nerve activi
ty (100% to 269+/-74%, P<.05) but did not increase mean arterial press
ure. In intact rabbits, we determined arterial baroreflex curves relat
ing renal sympathetic nerve activity and heart rate to mean arterial p
ressure by producing ramp increases (intravenous phenylephrine) and de
creases (intravenous nitroprusside) in mean arterial pressure. Cyclosp
orin A treatment produced a shift of the midrange of the baroreflex co
ntrol of heart rate (78.0+/-4.1 to 84.6+/0 4.7 mm Hg, P<.05) and renal
sympathetic nerve activity (74.6+/-3.9 to 87.0+/-4.8 mm Hg, P<.05). V
ehicle administration produced no effects on arterial baroreflex curve
s relating renal sympathetic nerve activity and heart rate to mean art
erial pressure. Compared with vehicle treatment, cyclosporin A reduced
the maximum gain of heart rate (-5.6+/-0.6 versus -3.1+/-0.8 beats pe
r minute per millimeter of mercury, P<.05) but had no effect on the ma
ximum gain of renal sympathetic nerve activity. In conscious sinoaorti
c-denervate rabbits, cyclosporin A had no effect on mean arterial pres
sure (95.7+/-7.3 to 91.8+/-10.8 mm Hg), renal sympathetic nerve activi
ty (100% to 110+/-6%), and heart rate (287+/-10 to 279+/-8 beats per m
inute). However, when the same sinoaortic-denervated rabbits were anes
thetized with sodium pentobarbital, cyclosporin A (20 mg/kg IV) produc
ed increases in renal sympathetic nerve activity (100% to 189+/-27%).
These data indicate (1) that the sympathoexcitatory response to cyclos
porin A depends on baroreceptor afferent input in the conscious state
and (2) that this response involves an upward resetting of the arteria
l baroreflex.