Abstract
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 ug, in the lateral cerebral ventricle (ICV) markedly and significantly (p < 0.05) increased the epinephrine dose, at the occurence of ventricular premature beats compared to the control group 228 ± 11 (SEM) vs 116 ± 7 ug epinephrine/kg and at the onset of fatal arrhythmias 225 ± 13 vs 185 ± 9 ug epinephrine/kg. Ang II, 0.5 ug 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 occured at 118 ± 4 ug epinephrine/kg. The Ang II receptor antagonist saralasin 150 ug/kg ICV, blunted and 300 ug/kg ICV reversed the effect of Ang II. The mu opioids antagonist naxolone and the kappa opioid antagonist MR 2266, 50 ug/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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.