Cardioacceleration provoked by intrathecal administration of vasoactive intestinal peptide (VIP): mediation by a non-central nervous system mechanism.
Intrathecal administration of VIP to the thoracic spinal cord in the urethane anaesthetized rat provoked a dose-dependent increase in heart rate without any change in arterial pressure. The cardioacceleration observed following administration of 6.5 nmol of VIP at the T9 level (n = 8) occurred within 1-2 min of administration, with a peak effect of 70-85 bpm, 10-30 min after administration. The magnitude of the maximum change when this dose was given at the T2 level (n = 8) was approximately 100 beats per min, 7-8 min after administration. However, the differences between T2 and T9 administration were not statistically significant. Intravenous administration of 6.5 nmol of VIP (n = 6) mimicked the cardioacceleratory effect of intrathecal administration, and also decreased systolic and diastolic arterial pressure by 9-13 mmHg 6-13 min after administration. The cardioacceleration observed following intrathecal administration at T9 was not blocked by prior systemic administration of the autonomic ganglion blocker hexamethonium (5 mg/kg) or by bilateral vagotomy. Nor was the effect blocked by prior intrathecal administration of the local anaesthetic lidocaine (250 micrograms), although lidocaine did block the tachycardia and hypertension resulting from intrathecal administration of substance P. Considered collectively, the findings that the cardioacceleration observed following intrathecal VIP injection is mimicked by i.v. administration, is not reversed by blockade of nicotinic transmission of autonomic ganglia or by bilateral vagotomy, and is not blocked by lidocaine suggest that VIP's tachycardic effect does not result from a direct action on spinal mechanisms mediating autonomic control of the cardiovascular system, but occurs via diffusion to a site of action outside the central nervous system.
Rochford
J
J
Department of Physiology, McGill University, Montreal, Quebec, Canada.
Henry
J L
JL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005725:Ganglia, Autonomic / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008012:Lidocaine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D009433:Neural Inhibition; D051381:Rats; D011919:Rats, Inbred Strains; D013373:Substance P / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*; D014660:Vasoactive Intestinal Peptide / Q000008:administration & dosage* / Q000494:pharmacology
D006584:Hexamethonium Compounds; D013373:Substance P; D014660:Vasoactive Intestinal Peptide; D008012:Lidocaine