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) elicited a bradycardia. This bradycardia was potentiated by the angiotensin converting enzyme inhibitor, captopril (1 mg kg-1, i.v.) by about 40%. Subsequent angiotensin II infusion (0.03 micrograms kg-1 min-1) reversed this effect. A similar facilitatory effect was also seen with the angiotensin receptor antagonist, losartan (10 mg kg-1, i.v.). These results suggest a tonic inhibitory effect of endogenous angiotensin II on vagal transmission. 2. The effect of captopril in potentiating vagal bradycardia appears to be at the level of vagal neurones, since the bradycardia elicited by the muscarinic agonist, methacholine was unaffected. 3. After the pithed rats were nephrectomized, captopril had no effect on vagally-induced bradycardia, suggesting that the formation of the endogenous angiotensin II responsible for the effect was dependent on renin release from the kidney. 4. When the sympathetic nerves of the pithed rat were electrically stimulated there was a tachycardia, and this was unaffected by captopril. However, when the sympathetic and vagus nerves were activated concurrently, the resulting tachycardia was inhibited 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 vagal 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-angiotensin drugs may attenuate the reflex tachycardia associated with the fall in blood pressure in anti-hypertensive therapy.
Rechtman
M
M
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Majewski
H
H
D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D016084:Bronchoconstriction / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D003655:Decerebrate State / Q000503:physiopathology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000294:innervation; D006339:Heart Rate / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D008688:Methacholine Compounds / Q000494:pharmacology; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology; D014403:Tubocurarine / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D001713:Biphenyl Compounds; D007093:Imidazoles; D008688:Methacholine Compounds; D013777:Tetrazoles; D000804:Angiotensin II; D002216:Captopril; D019808:Losartan; D014403:Tubocurarine