Evidence of Parasympathetic Activity of the Angiotensin Converting Enzyme Inhibitor, Captopril, in Normotensive Man

Abstract

Captopril (50 mg orally) produced a significant fall in systolic and diastolic blood pressure in six normotensive sodium replete subjects, without a rise in heart rate. On captopril, there was no change in the expected normal increase in heart rate on standing. Supine plasma noradrenaline was not reduced by captopril and normal postural increases were maintained. Atropine (0.04 mg/kg i.v.) reduced the difference in blood pressure change between captopril and placebo. Facial immersion in water produced a bradycardia. This change was abolished by atropine and attenuated both by captopril and edrophonium (10 mg i.v.), a cholinesterase inhibitor. Lying down after 6 min standing produced an immediate transient tachycardia, which was abolished by atropine and attenuated by captopril. Blood pressure and heart rate rose after a cold pressor test on both captopril and placebo. The tachycardia during the Valsalva manoeuvre was inhibited by edrophonium and to a lesser extent by captopril. The effects of captopril and edrophonium were additive. Parasympathetic activity of captopril may contribute to its haemodynamic profile.

The pharmacodynamics and dose‐response relationships of the angiotensin converting enzyme inhibitor, cilazapril, in essential hypertension.

“…The absence of reflex tachycardia with blood pressure reduction after ACE inhibitors appears, in part, to be related to an enhancement of cardiac parasympathetic tone (Sturani et al, 1982;Campbell et al, 1985;Ajayi et al, 1985a) following the withdrawal of the vagolytic actions of angiotensin II (Ajayi et al, 1985b).…”

The influence of cilazapril on indices of autonomic function in normotensives and hypertensives.

“…The absence of reflex cardioacceleration, even after acute dosing, suggests that ACE inhibitors exert some specific influence on, for example, autonomic reflex mechanisms or baroreflex integrity. There is no evidence to suggest that ACE inhibition significantly modifies either sympathetic tone or baroreflex function in man (Millar et al, 1982) but enhancement of-cardiac parasympathetic activity has been reported with captopril, enalapril and lisinopril (Sturani et al, 1982;Campbell et al, 1985;Ajayi et al, 1985a, b …”

The effect of enalapril on baroreceptor mediated reflex function in normotensive subjects.

“…The release of vagal pathways from angiotensin II mediated inhibition, both centrally and peripherally may well enhance cardiac parasympathetic tone, thus blunting the reflex tachycardia (Sturani et al, 1982;Ajayi et al, 1985a,b;Campbell et al, 1985).…”

“…Their focus was mainly on baroreceptor reflexes, hence their article somehow obscures other possible explanations for the absence of reflex cardioacceleration including (1) a central sympatho-inhibitory action, (2) removal of the peripheral angiotensin II (All) mediated presynaptic facilitation of noradrenaline release, (3) unchanged arterial wall tangential tension during ACE inhibition, (4) selective venodilatation or (5) parasympathetic activation. The relative merits of these propositions have been examined previously (Sturani etal., 1982;Ajayi etal., 1985 a,b;Campbell et al, 1985;Levenson et al, 1985).…”