Cyclosporine-induced sympathetic activation and hypertension after heart transplantation.
BACKGROUND
Hypertension is a frequent complication of cyclosporine-induced immunosuppression, but the underlying mechanism is unknown. In anesthetized animals, the administration of cyclosporine increases sympathetic-nerve discharge, which may contribute to hypertension.


METHODS
To determine whether cyclosporine-induced hypertension is accompanied by sustained sympathetic neural activation in patients, we recorded sympathetic action potentials using intraneural microelectrodes (in the peroneal nerve) in heart-transplant recipients receiving azathioprine and prednisone alone (n = 5) or in combination with cyclosporine (n = 14). We performed the same studies in eight patients with myasthenia gravis who were receiving cyclosporine and eight who were not, in five patients with essential hypertension, and in nine normal controls.


RESULTS
Heart-transplant recipients receiving cyclosporine had higher mean arterial blood pressure (+/- SE) than those not receiving cyclosporine (112 +/- 3 vs. 96 +/- 4 mm Hg; P less than 0.05) and a 2.7-fold higher rate of sympathetic-nerve firing (80 +/- 3 vs. 30 +/- 4 bursts per minute; P less than 0.05). For patients with myasthenia gravis, similar doses of cyclosporine were associated with smaller elevations in mean arterial blood pressure (100 +/- 2 mm Hg, as compared with 91 +/- 4 mm Hg in those not receiving cyclosporine; P less than 0.05) and in the rate of sympathetic-nerve firing (46 +/- 3 bursts per minute, as compared with 25 +/- 4 bursts per minute; P less than 0.05). Sympathetic activity in patients with heart transplants or myasthenia gravis who were not being treated with cyclosporine was no different from that in patients with essential hypertension or in normal controls.


CONCLUSIONS
Cyclosporine-induced hypertension is associated with sympathetic neural activation, which may be accentuated by the cardiac denervation that results from heart transplantation.
Scherrer
U
U
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-9034.
Vissing
S F
SF
Morgan
B J
BJ
Rollins
J A
JA
Tindall
R S
RS
Ring
S
S
Hanson
P
P
Mohanty
P K
PK
Victor
R G
RG
D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000187:drug effects; D003524:Cyclosporins / Q000009:adverse effects* / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000294:innervation; D016027:Heart Transplantation; D006801:Humans; D006973:Hypertension / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D009157:Myasthenia Gravis / Q000503:physiopathology; D009638:Norepinephrine / Q000097:blood; D011183:Postoperative Complications; D013564:Sympathetic Nervous System / Q000187:drug effects*
D003524:Cyclosporins; D009638:Norepinephrine