Studies on the cardiovascular effects produced by the spinal action of two substance P analogues in the rat: evidence for a central catecholaminergic mechanism.
The effects of two substance P (SP) analogues, [D-Trp7,9,10]SP (ana1) and [D-Pro4,Lys6,D-Trp7,9,10,Phe11]SP-(4-11) (ana2) on mean arterial pressure (MAP) and heart rate (HR) were measured following intrathecal administration at one of three spinal cord levels in rats anaesthetized with sodium pentobarbital. Following an initial increase, a profound and long-lasting fall in MAP and HR occurred when 6.5 nmol of either ana1 or ana2 was injected at T1-T3 or T8-T10. Only transient changes in MAP and a slight increase in HR was observed after injection of either peptide at L2-L4. The profound and long-lasting hypotension and bradycardia induced by ana1 were not significantly altered after intravenous injection of hexamethonium, phentolamine, propranolol, atropine, diphenhydramine, cimetidine, methysergide, naloxone or morphine. However, the biphasic effect of ana1 on MAP was prevented by the intrathecal administration of prazosin and yohimbine, suggesting that a central catecholaminergic mechanism including alpha 1- and alpha 2-adrenergic receptors is involved. The latter treatment did not prevent the tachycardia which occurred when the bradycardia was blocked, indicating that different mechanisms mediate the spinal action of ana1 on MAP and HR. Finally, cervical transection of the spinal cord eliminated the profound and long-lasting depressor effect of ana2, suggesting that a supraspinal mechanism is involved in this cardiovascular response.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000502:physiology*; D003655:Decerebrate State; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000187:drug effects* / Q000502:physiology; D013373:Substance P / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology
D002395:Catecholamines; D006584:Hexamethonium Compounds; D013373:Substance P