Angiotensin in the brain suppresses epinephrine-induced cardiac arrhythmias through CNS opioid mechanisms.
To test the hypothesis that angiotensin II (Ang II) in the central nervous system modulates catecholamine-induced cardiac arrhythmias and to determine whether endogenous opioids are operative in this action, arrhythmias were produced in male Wistar rats, by continuous infusion of epinephrine at incremental doses until the development of fatal arrhythmias that were usually ventricular fibrillation. Rats were instrumented with catheters in the lateral cerebral ventricle, femoral vein and femoral artery. Ang II, 0.5 microgram, in the lateral cerebral ventricle (ICV) markedly and significantly (p less than 0.05) increased the epinephrine dose, at the occurrence of ventricular premature beats compared to the control group 228 +/- 11 (SEM) vs 116 +/- 7 micrograms epinephrine/kg and at the onset of fatal arrhythmias 225 +/- 13 vs 185 +/- 9 micrograms epinephrine/kg. Ang II, 0.5 microgram i.v., did not affect arrhythmia threshold. The angiotensin converting enzyme inhibitor captopril, 1 mg/kg, decreased arrhythmia threshold as ventricular arrhythmias were first noted at 106 +/- 4 and fatal arrhythmias occurred at 118 +/- 4 micrograms epinephrine/kg. The Ang II receptor antagonist saralasin 150 micrograms/kg ICV, blunted and 300 micrograms/kg ICV reversed the effect of Ang II. The mu opioids antagonist naloxone and the kappa opioid antagonist MR 2266, 50 micrograms/kg ICV, prevented the effect of Ang II on fatal arrhythmias. The action Ang II on arrhythmias could not be explained by the effects of Ang II on blood pressure or heart rate. These data indicate a role for Ang II within the CNS to modulate cardiac arrhythmias and that this is mediated in part, by endogenous opioids.
Rabkin
S W
SW
University of British Columbia, Vancouver, Canada.
D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000502:physiology*; D002216:Captopril / Q000494:pharmacology; D004837:Epinephrine / Q000037:antagonists & inhibitors; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009292:Narcotic Antagonists / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D012504:Saralasin / Q000494:pharmacology
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D000804:Angiotensin II; D002216:Captopril; D012504:Saralasin; D004837:Epinephrine