Stein CM, He H, Pincus T, Wood AJJ
Cyclosporine impairs vasodilatation without increased
sympathetic activity in humans
(Oct) 26:705-710 1995
Two potential mechanisms for cyclosporine induced hypertension
include enhanced sympathetic tone (Scherrer et al, NEJM 323:693,
1990) and enhanced vasoconstriction. Here 12 patients with
rheumatoid arthritis receiving cyclosporine were studied, once on
and once off the drug. Venodilatation was assessed using a
dorsal hand vein method, measuring changes in vein diameter in
response to infusion of vasoconstricting or vasodilating agents.
Cyclosporine had no effect on the constricting effect of
phenylephrine. Venodilation in response to isoproterenol and
PGE-1 was markedly impaired when the patients were on
cyclosporine, whereas the dilatory response to nitroglycerine was
similar. Interestingly, response to isoproterenol was still
impaired in 5 patients (who had received cyclosporine for 6-12
months) after being off the drug for 1 month. This points to a
potential prolonged effect of cyclosporine on the vasculature.
Sympathetic activity was measured by the spillover technique.
Tritiated NEPI is infused and the venous blood is analyzed for
rate of norepinephrine release into plasma. Cyclosporine had no
effect on NEPI spillover.
Comment: The Scherrer study measured sympathetic
activation directly, by peroneal nerve microneurography. Thus
this paper does not negate the Scherrer data (in cardiac
transplant recipients) that cyclosporine may induce sympathetic
activation. However, the data suggesting a "direct" vascular
effect are interesting.Daugirdas
Additional comments by J.G. Umans:
Mechanisms for the frequent and difficult to control hypertension which
often occurs in patients receiving cyclosporine A remains obscure. Species
differences and limited ability to extrapolate from many in vitro models
have limited mechanistic insights. This study suggests some defect in
vasodilation following cyclosporine, but provides little mechanistic insight
as to how vasodilation may be impaired.
Indeed, we learn neither the cells nor mediators which might be involved. As
well, one must be circumspect in extrapolating from the reactivity of a small
subset of capacitance vessels to those small arterial vessels which
may contribute to systemic resistance or to the renal regulation of blood
pressure. This in vivo human study provides yet another insight to our
still-limited understanding of this particular drug-induced blood pressure
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Renal transplant patients