Although intravenous cyclosporine A (CsA) previously has been shown to
cause a robust sympathetically mediated increase in blood pressure in
the rat, the underlying mechanism by which CsA increases the activity
of the sympathetic nervous system is unknown. To determine the relati
ve contributions of central neural versus peripheral reflex mechanisms
in causing this sympathetic activation, we recorded efferent renal sy
mpathetic nerve activity and blood pressure during intracerebroventric
ular or intravenous infusion of CsA, the latter performed in intact ra
ts and in those with sinoaortic denervation, cervical or subdiaphragma
tic vagotomy, or dorsal rhizotomy (T-10 through L(1)). In intact rats,
intravenous CsA (5 mg/kg), as expected, tripled renal sympathetic ner
ve activity and increased mean arterial pressure by 27+/-4 mmHg (P<.05
). The new findings are that this sympathoexcitatory effect of intrave
nous CsA (1) was not duplicated by central administration (either into
the cerebroventricular system or directly onto the ventrolateral surf
ace of the medulla), (2) was unaffected by sinoaortic denervation, but
(3) was greatly attenuated by either cervical or subdiaphragmatic vag
otomy or by dorsal rhizotomy. In additional experiments, we found that
intravenous cyclosporine increased the multiunit activity of subdiaph
ragmatic but not cardiopulmonary vagal afferents. From these data, we
conclude that in the rat CsA-induced increases in sympathetic activity
and blood pressure are caused mainly by activation of excitatory neur
al reflexes arising in the subdiaphragmatic region. These reflex mecha
nisms use at least two different afferent neural pathways: one involvi
ng the subdiaphragmatic vagi and the other involving the low thoracic
dorsal spinal roots.