Cardiovascular interactions between methionine-enkephalin and substance P in the conscious dog

Interactions between the undecapeptide Substance P (SP) and the pentapeptide methionine-enkephalin (Met5-ENK) have been described in isolated organ systems and in baroreceptor reflex mechanisms. Previous studies in our laboratory have demonstrated that systemically injected Met5-ENK simultaneously increases mean systemic arterial pressure (MAP) and heart rate (HR) in the conscious, chronically instrumented dog. We have now evaluated cardiovascular interactions between SP and Met5-ENK. In this model, SP injected intravenously produces a rapid and transient decrease in MAP and increase in HR over the dose range from 1.0 to 10.0 ng/kg. SP does not appear to appreciably alter subsequent responses to Met5-ENK. At SP doses of 1.0 ng/kg, the peak hemodynamic response to SP and Met5-ENK (35 micrograms/kg) given together appears to represent a simple summation effect of both drugs on HR and MAP. However, at higher SP doses (5.0 ng/kg), the SP response predominates and is little altered by the presence of Met5-ENK. Thus, Met5-ENK does appear capable of modulating the hemodynamic responses to SP over certain dose ranges.