Ischaemia-induced sympathoexcitation in spinalyzed rats

Abstract

Systemic ischaemia increases sympathetic activity via both reflex and direct effects on the nervous system, which include the hypothalamus and brainstem structures that provide excitatory drive to sympathetic pre-ganglionic motoneurones. Using an arterially perfused working heart-brainstem preparation (WHBP), we evaluated the sympathoexcitatory response recorded from the thoracic sympathetic chain (tSC) in response to systemic ischaemia (produced by arresting perfusion for 30 s) before and after transecting consecutively at both the ponto-medullary and medullary-spinal cord junctions. Ischaemia produced a striking increase in tSC activity that persisted after transecting at both the ponto-medullary and medullary-spinal cord levels (intact: 70+/-3%; ponto-medullary: 77+/-7%; medullary-spinal cord: 61+/-6%; n=9). In sino-aortic denervated (SAD) rats (n=4), sympathoexcitatory responses were smaller in both intact and ponto-medullary, but not in medullary-spinal cord transected versus intact rats. Following administration of a ganglionic blocker [hexamethonium (hex), 25 mg/kg] after medullary-spinal cord transection the ischaemia-induced sympathoexcitatory response was reduced (12+/-6% increase relative to control, n=4). In medullary-spinal cord transected preparations, intrathecal injection of N2-saturated saline increased tSC discharge (22+/-3%, n=4), which was attenuated by hex (5+/-1%). We propose that neural mechanisms within the cervical-thoracic segments can make a substantial contribution to the sympathoexcitatory response during systemic ischaemia.