Sympathoexcitatory Response to Cyclosporin A and Baroreflex Resetting

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 nerve electrodes. In intact rabbits, cyclosporin A (20 mg/kg IV, 30 minutes) produced significant increases in renal sympathetic nerve activity (100% to 269 +/- 74%, P < .05) but did not increase mean arterial pressure. In intact rabbits, we determined arterial baroreflex curves relating renal sympathetic nerve activity and heart rate to mean arterial pressure by producing ramp increases (intravenous phenylephrine) and decreases (intravenous nitroprusside) in mean arterial pressure. Cyclosporin A treatment produced a shift of the midrange of the baroreflex control of heart rate (78.0 +/- 4.1 to 84.6 +/- 4.7 mm Hg, P < .05) and renal sympathetic nerve activity (74.6 +/- 3.9 to 87.0 +/- 4.8 mm Hg, P