The influence of the inter-dose time interval on the cardiovascular response to methionine-enkephalin in the conscious dog.

Intravenous injection of methionine-enkephalin (10 micrograms/kg) into the conscious dog increased both heart rate and mean systemic arterial pressure. Progressive shortening of the inter-dose time interval from 5 min to 1 min and then to 30 sec did not alter the response, as the maximal mean systemic arterial pressure elevation was maintained and the maximal heart rate response increased slightly. In contrast to the results after discrete bolus dosing, continuous infusion of methionine-enkephalin at a constant rate of 10 micrograms/kg/min produced an initial elevation in heart rate and mean arterial pressure, but these parameters then began to return toward pretreatment levels despite continuous infusion at the same rate, indicating receptor desensitization. This desensitization pattern is most compatible with receptors of the nicotinic-cholinergic type. These data indicate the importance of dosing techniques in assessing cardiovascular responses to systemically administered enkephalins.