Circulation, Vol 88, 1101-1109, Copyright © 1993 by American Heart Association
D Kaye, J Thompson, G Jennings and M Esler
BACKGROUND. Hypertension frequently complicates the use of cyclosporine A
(CyA) therapy, and it has been suggested that sympathoexcitation may be the
underlying mechanism in this form of hypertension. METHODS AND RESULTS. To
further investigate the possibility of a neurogenic mechanism for this
hypertensive effect, we studied the effects of CyA on renal blood flow (n =
11), forearm blood flow (n = 8), and sympathetic nervous system activity,
assessed by renal and whole-body radiolabeled norepinephrine plasma
kinetics and muscle sympathetic nerve firing (using microneurography) in
cardiac transplant recipients receiving CyA and a reference group of
healthy age-matched control subjects (n = 17). In 11 cardiac transplant
patients (2 hours after cyclosporine dose), renal blood flow was
significantly lower than that in 8 control subjects (680 +/- 88 vs 1285 +/-
58 mL/min, P < .001). In 5 of these transplant patients, renal blood
flow was measured before and for 2 hours after oral cyclosporine and fell
progressively over this period, by 37% (P < .01). Total body and renal
norepinephrine spillover rates in transplant patients were similar to those
in control subjects (3070 +/- 538 vs 2618 +/- 313 pmol/min and 579 +/- 124
vs 573 +/- 95 pmol/min, respectively), and there was no progressive effect
in the 2 hours after cyclosporine dosing. Forearm blood flow was increased
2 hours after CyA administration (1.74 +/- 0.31 to 3.12 +/- 0.50 mL x 100
mL-1 x min-1, P < .001), whereas mean arterial blood pressure and
noninvasively determined cardiac output (indirect Fick method) were
unchanged. Muscle sympathetic nerve discharge rates recorded in 6 of these
transplant patients were not different from those in 9 healthy control
subjects (37.9 +/- 10.1 vs 41.3 +/- 2.3 bursts per 100 beats per minute).
During 90 to 120 minutes of recording after cyclosporine dosing, nerve
firing rates remained unchanged. CONCLUSIONS. CyA therapy causes acute
renal vasoconstriction without accompanying systemic hemodynamic effects.
These renal effects are nonneural, not being attributable to
sympathoexcitation.
ARTICLES
Cyclosporine therapy after cardiac transplantation causes hypertension and renal vasoconstriction without sympathetic activation
Alfred and Baker Medical Unit, Alfred Hospital, Prahran, Victoria, Australia.
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