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.
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006145:Guanethidine / Q000494:pharmacology; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011950:Receptors, Cholinergic / Q000187:drug effects; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013373:Substance P / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000494:pharmacology; D013610:Tachycardia / Q000139:chemically induced*
D011950:Receptors, Cholinergic; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P; C042867:spantide; D011433:Propranolol; D006145:Guanethidine