A FACILITATORY EFFECT OF ANTI-ANGIOTENSIN DRUGS ON VAGAL BRADYCARDIA IN THE PITHED RAT AND GUINEA-PIG

1 In pithed rats, preganglionic vagal nerve stimulation (at 5 Hz) elic ited a bradycardia. This bradycardia was potentiated by the angiotensi n converting enzyme inhibitor, captopril (1 mg kg-1, i.v.) by about 40 %. Subsequent angiotensin II infusion (0.03 mug kg-1 min-1) reversed t his effect. A similar facilitatory effect was also seen with the angio tensin receptor antagonist, losartan (10 mg kg-1, i.v.). These results suggest a tonic inhibitory effect of endogenous angiotensin II on vag al transmission. 2 The effect of captopril in potentiating vagal brady cardia appears to be at the level of vagal neurones, since the bradyca rdia elicited by the muscarinic agonist, methacholine was unaffected. 3 After the pithed rats were nephrectomized, captopril had no effect o n vagally-induced bradycardia, suggesting that the formation of the en dogenous angiotensin II responsible for the effect was dependent on re nin release from the kidney. 4 When the sympathetic nerves of the pith ed rat were electrically stimulated there was a tachycardia, and this was unaffected by captopril. However, when the sympathetic and vagus n erves were activated concurrently, the resulting tachycardia was inhib ited by captopril. 5 In pithed guinea-pigs, captopril also potentiated the bradycardia caused by vagal nerve stimulation. This appears to be a tissue-selective effect since the bronchoconstriction due to the va gal stimulation was not affected by captopril. 6 These results suggest that endogenous angiotensin II can have a tonic inhibitory effect on cardiac vagal transmission. Disruption of this mechanism by anti-angio tensin drugs may attenuate the reflex tachycardia associated with the fall in blood pressure in anti-hypertensive therapy.