Autonomic effects of central injections of D-Ala2-Met-enkephalinamide (DAME) in the conscious monkey.
The use of naloxone (NAL), an opioid receptor antagonist, has provided indirect evidence that endogenous opioids contribute to cardiovascular depression during shock. To determine if endogenous opioids act centrally to influence cardiovascular function, injections of D-Ala2-Met-enkephalinamide (DAME), a potent Met-enkephalin analog, were made into the 3rd cerebral ventricle (ICV) of 5 conscious cynomulgus monkeys restrained in primate chairs. Systolic blood pressure (SBP) and heart rate (HR) were determined every 10 min during a 30-60 min control period and for up to 5 hr post-injection. Colonic temperature (Tc) was monitored continuously. SBP declined from baseline values with 50 and 100 micrograms (85.2 and 170.4 nM) doses but was significant (p less than 0.001) for only the 100 micrograms dose between 15-125 min post-injection. HR also decreased but did not exhibit any significant variation with time. However, when averaged across time, HR fell significantly (p less than 0.001) from baseline: -9.1 +/- 2.3 and -15.0 +/- 2.1 b/min for 50 and 100 micrograms DAME, respectively. Tc displayed a nonsignificant, delayed (greater than 2 hr) rise in Tc with the 50 micrograms dose, whereas the 100 micrograms dose caused a significant (p less than 0.001) decline in Tc (from 65-125 min post-injection). NAL injected ICV attenuated the effects of DAME but had no effect on SBP, HR or Tc when injected alone. Systemic injection of DAME (300 micrograms) in one monkey produced a transient decline in SBP (26 mmHg within 2 min) which returned to baseline values 4 min post-injection. HR and Tc were unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects*; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004744:Enkephalin, Methionine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D008252:Macaca fascicularis; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D013997:Time Factors
D009270:Naloxone; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-