Angiotensin II type 1 receptors may not influence response of spinal autonomic neurons to axonal damage

Objectives: Angiotensin II can promote cell stress, and the expression of its AT₁ receptor is characteristic of neuronal populations that die off in multiple systems atrophy and Parkinson's disease. To explore the possible significance of these facts, we undertook to: (1) clarify the distribution of AT₁ in rat neurons; (2) use selective antagonists as a means of determining whether AT₁ activation predisposes stressed neurons to die. Methods: AT₁-expression was examined by immunohistochemistry and by autoradiography for [¹²⁵l]-sarcosine¹-angiotensin II binding in sensory, motor and autonomic neurons. To induce cell loss in a specific neuronal population, rats were given systemic i.v. injection of anti-acetylcholinesterase antibodies, which cause a delayed death of pre-ganglionic sympathetic neurons in the intermediolateral nucleus (IML). As pharmacologic intervention, some immunolesioned rats were treated with the selective AT₁ antagonist, Candesartan. Results: Immunohistochemistry and autoradiography revealed AT₁ expression in dorsal root ganglia, superior cervical ganglion. In the dorsal horn of the spinal cord, AT ₁ immunostainining and angiotensin binding were both prominent. In ventral horn and IML, immunoreactivity for AT₁ and choline acetyltransferase co-localized in pre-ganglionic sympathetic and somatic motor neurons. Immunolesion caused over 50% loss of IML perikarya within 3 months. Concurrent treatment with the AT₁ antagonist, Candesartan, did not affect the outcome. Discussion: AT₁ expression is surprisingly widespread in sensory, autonomic and somatic motor neurons of the rat. This expression may be important to the normal physiology of these systems. Present data, however, do not support the concept that AT₁ activation contributes to the loss of autonomic neurons after axonal damage.