Enkephalin inhibits vagal control of heart rate, contractile force and coronary blood flow in the canine heart in vivo.

摘要

The following studies were conducted to determine if the ability of the intrinsic cardiac opioid, met-enkephalin-arg-phe to interrupt vagal bradycardia can be generalized to include the disruption of vagal effects on atrial contraction and coronary blood flow. Anesthetized dogs were instrumented to measure heart rate and left atrial contractile force or heart rate and coronary blood flow. The response of each variable was recorded at rest and during vagal stimulation. During the evaluation of vagal effects on contractile activity and coronary blood flow, heart rate was maintained constant by electrically pacing the hearts above their resting heart rate. In the first protocol, vagal stimulation reduced both heart rate and atrial contractile force in a frequency dependent fashion. When met-enkephalin-arg-phe (MEAP) was infused systemically for three min at 3 nmol min(-1) kg(-1), there were no observed changes in resting heart rate or atrial contraction. However, when the vagal stimuli were reapplied during the peptide infusion, the previously observed vagal effects on rate and contractile force were reduced in magnitude by one-half to two-thirds. The ability of MEAP to interrupt the vagal control of heart rate and contractile activity involves opiate receptors since the effect was eliminated in both cases by prior opiate receptor blockade with the high affinity antagonist, diprenorphine. In the second protocol, vagal stimulation produced a transient increase in coronary blood flow and an accompanying increase in myocardial oxygen consumption. These effects were reduced by approximately 80% during the systemic infusion of MEAP. A similar increase in coronary blood flow mediated by the direct acting muscarinic agonist, methacholine, was unaltered by the infusion of peptide. In summary, these data suggest that the intrinsic cardiac enkephalin, MEAP, is capable of inhibiting the vagal control of heart rate, contractile force and coronary blood flow and probably does so through a common opiate receptor located prejunctionally on vagal nerve terminals or within nearby parasympathetic ganglia.