The cardiovascular effects of centrally administered substance P in the anaesthetised rabbit

The cardiovascular effects of Substance P (SP) administered into the cisterna magna (i.c.) of the pentobarbitone anaesthetised rabbit have been investigated. SP given i.c. in low doses (0.2-10 ng/kg) caused a dose related rise in blood pressure and bradycardia. Both responses were attenuated by pretreatment with intravenous (i.v.) pentolinium. SP given i.v. (1 ng/kg-1 microgram/kg) caused a dose related fall in pressure and tachycardia. The pressor response observed after i.c. administration was reduced by pretreatment with morphine and enhanced by naloxone. Bilateral sinoaortic denervation also enhanced the pressor effect of SP, but after deafferentation naloxone had no further effect. Pretreatment with clonidine abolished this rise in pressure. It is concluded that the central administration of SP has a direct pressor effect whereas the bradycardia appears to result from both direct and indirect effects, leading to a decrease in cardiac sympathetic activity. Both actions are mediated by the autonomic nervous system. SP may be involved in the central regulation of blood pressure and modulation of baroreceptor reflex activity.