Cyclosporine causes sympathetically mediated elevations in arterial pressure in rats.
Cyclosporine-induced immunosuppression has emerged as a new cause of hypertension, but the underlying mechanisms are poorly understood. In patients, this hypertension is accompanied by sympathetic neural activation. We therefore hypothesized that increased sympathetic nerve discharge is an important mechanism by which cyclosporine raises blood pressure. To test this hypothesis, we examined effects of acute administration of cyclosporine (5 mg/kg i.v.) or vehicle on renal and lumbar sympathetic nerve activity, renal and femoral blood flow velocity (pulsed Doppler flowmetry), and arterial pressure in chloralose-anesthetized rats. Vehicle had no effect on sympathetic nerve activity, whereas cyclosporine caused renal and lumbar sympathetic nerve activity to increase progressively over 60 minutes to levels that were 362 +/- 46% and 388 +/- 70%, respectively, of the baseline values (p less than 0.05). These increases in sympathetic nerve activity were accompanied by proportional increases in renal and femoral vascular resistance and sustained increases in mean arterial pressure (+19 +/- 3 mm Hg, p less than 0.05 versus baseline). The cyclosporine-induced increases in regional vascular resistance and arterial pressure were greatly attenuated, or abolished, by ganglionic blockade or by clonidine (central sympatholysis) but were unaffected by angiotensin converting enzyme inhibition. These findings demonstrate that in an anesthetized animal preparation, the vasoconstrictor and blood pressure-raising effects of cyclosporine are caused by sympathetic neural activation.
Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas 75235-9034.
B J
BJ
Morgan
T
T
Lyson
U
U
Scherrer
R G
RG
Victor
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects
D016572:Cyclosporine