Centrally mediated enhancement of ouabain cardiotoxicity by angiotensin II in dogs.
The effect of angiotensin II (Ang II) infusion on the doses of ouabain required to induce ventricular arrhythmias and death was investigated in anesthetized dogs. Tritiated ouabain was infused alone i.v. (1 microgram/kg per min) to establish the control toxic doses and the level of ouabain in the heart at death. When Ang II and ouabain were co-infused i.v. the doses of ouabain needed to induce arrhythmias and death were significantly reduced. Spinal transections performed at C-1 prior to drug infusions prevented the effect of Ang II to enhance the toxicity of ouabain. Thus, the action of Ang II to augment ouabain toxicity appeared to be related to its effects on the sympathetic nervous system. To confirm that Ang II was acting within the brain rather than at peripheral sites of the sympathetic system, Ang II was infused into the vertebral artery of spinal cord intact dogs. The infusion rate of Ang II needed to produce a significant enhancement of ouabain toxicity was much lower when given into the vertebral artery than into the femoral vein. These data indicate that Ang II enhances the cardiotoxicity of ouabain via an action produced within the brain and mediated by the sympathetic nervous system.
D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005260:Female; D006321:Heart / Q000187:drug effects*; D007263:Infusions, Parenteral; D007269:Injections, Intra-Arterial; D008297:Male; D009206:Myocardium / Q000032:analysis; D010042:Ouabain / Q000032:analysis / Q000633:toxicity*; D013116:Spinal Cord / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects
D000804:Angiotensin II; D010042:Ouabain