Cyclosporine-induced hypertension: evidence for maintained baroreflex circulatory control.
BACKGROUND
The clinical use of cyclosporine as an immunosuppressive agent enhanced long-term survival in transplant recipients at the expense of a high incidence of induced hypertension. Altered neurovegetative (autonomic) cardiovascular control is suspected as a mechanism of this form of hypertension.


METHODS
Spectral analysis of systolic arterial pressure and R-R interval variability (electrocardiographic recordings) were performed, and the index alpha of baroreflex gain was computed in four groups of subjects matched for age: 13 orthotopic heart transplant recipients; 13 solid organ transplant recipients; 13 patients with essential hypertension; and 18 control subjects with normal blood pressure. All but the control subjects were treated with similar dihydropyridine calcium entry blockers. Heart and solid organ transplant recipients also received cyclosporine.


RESULTS
R-R variance was lowest in the heart transplant recipients. The spectral profile of R-R interval was suggestive of sympathetic predominance in the patients with hypertension, but not in the solid organ transplant recipients or the control subjects. Systolic blood pressure variability and low frequency component (a marker of sympathetic vasomotor modulation) were similar in the four groups. The index alpha was 1.8 +/- 2.2 in heart transplant recipients, 11.7 +/- 6.6 in solid organ transplant recipients, 7.3 +/- 3.6 in patients with hypertension, and 13.5 +/- 6.4 msec/mm Hg in control subjects (p = 0.0001).


CONCLUSIONS
These data indicate that (1) cyclosporine-induced hypertension in heart transplant recipients is associated with a loss of baroreflex function as a result of cardiac denervation-related uncoupling; (2) compared with patients with hypertension, organ transplant recipients with hypertension demonstrated a maintained baroreflex function as indicated by a lack of reduction of the index alpha; (3) baroreflex heart rate control in dihydropyridine-treated cyclosporine-induced hypertension is well maintained.
Lucini
D
D
Department of Internal Medicine, Ochsner Medical Institutions, New Orleans, Louisiana 70121, USA.
Milani
R V
RV
Ventura
H O
HO
Mehra
M R
MR
Messerli
F H
FH
Murgo
J P
JP
Regenstein
F
F
Copley
B
B
Malliani
A
A
Pagani
M
M
D000328:Adult; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D016572:Cyclosporine / Q000009:adverse effects* / Q000627:therapeutic use; D003714:Denervation; D004359:Drug Therapy, Combination; D004562:Electrocardiography / Q000187:drug effects; D005260:Female; D006321:Heart / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000139:chemically induced* / Q000503:physiopathology; D007166:Immunosuppressive Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000139:chemically induced* / Q000503:physiopathology; D011311:Pressoreceptors / Q000187:drug effects* / Q000502:physiology; D012018:Reflex / Q000187:drug effects* / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology; D014630:Vagus Nerve / Q000187:drug effects / Q000503:physiopathology
D007166:Immunosuppressive Agents; D016572:Cyclosporine