ANTIARRHYTHMIC EFFECTS OF CYCLIC GUANOSINE 3'-5'-MONOPHOSPHATE AND SODIUM-NITROPRUSSIDE ON BARIUM-CHLORIDE ARRHYTHMIAS IN RABBITS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 257  (2) , 225-238
Abstract
The hypothesis that cGMP and sodium nitroprusside (NP), an activator of guanylate cyclase which elevates levels of cGMP, have antiarrhythmic activity was tested in the BaCl2 model of arrhythmias. ECG were recorded continuously on tape in unanesthetized New Zealand white rabbits weighing .apprx. 2.0 kg. BaCl2 (4 mg/kg i.v. bolus) induced frequent ventricular ectopic beats. These ventricular arrhythmias were abolished by 8-bromo-cGMP (5 mg/kg) injected into the left ventricle (5/6 rabbits), NP 25.0 .mu.g/kg per min i.v. (6/6), NP 10 .mu.g/kg per min i.v. (3/6), and markedly reduced in frequency by NP 10 .mu.g/kg per min (3/6). In temporal association with NP, 4-fold increases in cGMP levels in blood and significant increases in myocardial GMP were found compared to control animals (n = 6). In this model, cGMP and NP have significant antiarrhythmic properties. NP effect may be mediated by alterations in cGMP metabolism.