Differential effects of acute and sustained cyclosporine and tacrolimus on sympathetic nerve activity.
BACKGROUND
We studied the effect of acute and sustained cyclosporine and tacrolimus on muscle sympathetic nerve activity (MSNA) in groups of healthy male volunteers.


RESULTS
Acute cyclosporine in normal dose (2.5 mg/kg) increased MSNA from 11 +/- 6 to 19 +/- 8 bursts/min (P < 0.05). Acute cyclosporine in high dose (10 mg/kg) increased MSNA from 13 +/- 6 to 25 +/- 4 bursts/min (P < 0.05) and increased heart rate and mean arterial pressure (heart rate from 64 +/- 8 to 74 +/- 6 b.p.m., MAP from 92 +/- 10 to 105 +/- 8 mmHg; both P < 0.05). Sustained cyclosporine (2.5 mg/kg b.i.d. for 2 weeks) suppressed MSNA from 14 +/- 6 to 8 +/- 7 bursts/min (P < 0.05). Blood pressure increased from 89 +/- 6 to 98 +/- 6 mmHg (P < 0.05). Body weight increased and plasma renin activity was suppressed. Acute tacrolimus in regular dose (0.05 mg/kg) and high dose (0.20 mg/kg) had no effect on MSNA and blood pressure. Sustained tacrolimus (0.05 mg/kg b.i.d. for 2 weeks) had no effect on blood pressure, body weight and plasma renin activity, but decreased MSNA from 14 +/- 6 to 8 +/- 5 bursts/min (P < 0.05).


CONCLUSIONS
Sympathetic overactivity plays a role in the acute hypertensive action of cyclosporine. Cyclosporine given during 2 weeks increases blood pressure and suppresses MSNA, possibly by volume retention. Tacrolimus, in the presently applied dosages, does not cause hypertension or sympathetic overactivity. However, sustained tacrolimus also suppresses sympathetic activity, the reason of which is unclear.
Klein
Inge H H T
IH
Department of Nephrology and Hypertension, University Medical Center, Utrecht, The Netherlands.
Abrahams
Alferso C
AC
van Ede
Thomas
T
Oey
P Liam
PL
Ligtenberg
Gerry
G
Blankestijn
Peter J
PJ
D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D065095:Calcineurin Inhibitors; D016572:Cyclosporine / Q000008:administration & dosage* / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology*; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D012083:Renin / Q000097:blood; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000503:physiopathology*; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects*
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D012083:Renin; D016559:Tacrolimus