Cyclosporine therapy after cardiac transplantation causes hypertension and renal vasoconstriction without sympathetic activation.
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.
- Copyright © 1993 by American Heart Association