S. Gotze et al., PREVENTIVE EFFECTS OF DILTIAZEM ON CYCLOSPORINE-A-INDUCED VASCULAR SMOOTH-MUSCLE DYSFUNCTION, Transplant international, 7(3), 1994, pp. 157-162
Cyclosporin A may cause vascular smooth muscle dysfunction due to calc
ium overload as a consequence of chronically augmented calcium influx.
In the present study, the responsiveness to vasoconstrictors was inve
stigated in rats after chronic treatment for 6 weeks with placebo, cyc
losporin A (30 mg/kg per day), diltiazem (60 mg/kg per day), or cyclos
porin A plus diltiazem. Twenty-four hours after the last oral treatmen
t the animals were sacrified and rings of the thoracic aorta were susp
ended in organ chambers under isometric conditions in the absence of c
yclosporin A or diltiazem. Chronic treatment with cyclosporin A signif
icantly augmented contractions to angiotensin II (10 10(-5) M). This e
ffect was prevented by cotreatment with diltiazem. Diltiazem did not a
ffect the cyclosporin A-induced reduction in the response to potassium
chloride (10-80 mM) The contractions to phenylephrine (10(-9)-10(-6)
M) and endothelin-1 (10(-9)-10(-7) M) were not significantly different
in the four groups. The preventive effect of diltiazem against the cy
closporin A-induced hypersensitivity to angiotensin II supports the hy
pothesis of increased calcium influx during cyclosporin A therapy. The
results may provide an additional rationale for the use of calcium an
tagonists in the treatment of the vascular side effects of cyclosporin
A.