Substance P-induced tachycardia in the anaesthetized rat

In pentobarbital-chloralose-anaesthetized rats, pretreated with hexamethonium and atropine the mechanism by which substance P (SP) causes tachycardia was analysed. Substance P, when infused i.v. at doses between 0.49 nmol and 1.52 nmol elicited a marked, dose-dependent tachycardia, which was reduced to less than half by propranolol, 0.1 mg kg-1. Furthermore, the SP-induced tachycardia was reduced to about 1/10 of control by guanethidine. Further, the tachycardia, which could also be elicited in pithed rats, was antagonized by the SP-receptor blocker Spantide, but these results must be taken with care since Spantide itself caused a pronounced and long-lasting depressor response. It is hypothesized that SP causes tachycardia by exciting specific receptors on the stellate ganglia, which leads to an activation of adrenergic fibres to the sinus node.