Angiotensin II modulates cardiovascular autonomic control in the absence of baroreflex loading

Abstract

Objective-To investigate the eVects of angiotensin II in the absence of baroreflex activation. Design-Ten healthy male volunteers were studied in a single blind, randomised, crossover study of heart rate variability during intravenous angiotensin II infusion (5-20 ng/kg/min) compared with a control pressor infusion of phenylephrine (0.7-2.8 µg/kg/min). Each infusion was titrated to increase mean blood pressure by 20 mm Hg; sodium nitroprusside was then infused simultaneously to restore blood pressure to baseline values. Conclusions-When the pressor response is controlled by sodium nitroprusside, angiotensin II infusion is associated with tachycardia. Analysis of heart rate variability suggests that this reflects inhibition of cardiac vagal activity. (Heart 1998;80:127-133) Keywords:angiotensin II; heart rate variability; autonomic nervous system; parasympathetic nervous system Results-DuringThe important pathophysiological eVects of angiotensin II in congestive heart failure and after myocardial infarction have been amply demonstrated by the reduction in mortality seen in trials of angiotensin converting enzyme inhibitors and more recently, angiotensin II antagonists.1-3 The results cannot be explained by haemodynamic actions alone as other vasodilators are less eVective.4 5 We have previously suggested that the explanation may lie in the adverse eVects of angiotensin II on cardiac autonomic nervous control. There is strong evidence that impaired cardiac autonomic function is associated with an adverse prognosis after myocardial infarction and in heart failure, 8 9 and animal experiments have shown that angiotensin II has direct eVects on both vagal and sympathetic nervous control. Inhibition of cardiac vagal activity by circulating angiotensin II is mediated both centrally 10 and peripherally. 11 There is also evidence of facilitatory eVects on sympathetic nervous activity.12 Most of this work has been performed in anaesthetised animals, making it diYcult to draw conclusions which can be applied reliably to humans.Investigation of the eVect of angiotensin II on cardiac autonomic activity in intact conscious animals and in humans is hampered by baroreflex activation caused by its powerful pressor eVect. One approach has been to control for the pressor eVect by comparing the results of angiotensin II infusion with those resulting from a control pressor agent such as phenylephrine. In dogs, little increase in vagal activity occurred during angiotensin II infusion despite the rise in arterial pressure; in contrast there was a marked increase in vagal activity during control pressor infusion of phenylephrine. 13 In humans, the baroreceptor heart rate reflex is similarly inhibited by angiotensin II.7 14 This does not appear to result from facilitation of sympathetic tone, as tritiated noradrenaline kinetic studies showed no significant diVerence in sympathetic activity during angiotensin II infusion and during an equipressor infusion of phenylephrine. 15In a previous study using analysis of heart rate v...

Effects of angiotensin II (AT1) receptor blockade on cardiac vagal control in heart failure

“…Central and peripheral actions resulting in inhibition of cardiac parasympathetic control and facilitation of sympathetic activity have been demonstrated in animals [6][7][8]. In humans, our studies have shown that cardiac vagal control is reduced by angiotensin II [3], and a facilitatory action on the baroreflex control of sympathetic activity has also been described [27]. These actions appear to be mediated by AT " receptors [28], and therefore pharmacological blockade might be expected to increase measures of cardiac vagal activity and reduce those related to sympathetic activity.…”

“…These effects may be mediated both centrally and peripherally. In healthy human volunteers, we have shown previously that exogenous angiotensin II reduces the cardiac vagal modulation of heart rate [3]. Conversely, we and others have shown that, in patients with heart failure, indices of cardiac vagal activity are increased by ACE inhibitors [9][10][11][12].…”

“…The effects of ACE inhibitors on mortality cannot be explained by haemodynamic actions alone, since other vasodilators are less effective [1]. We have suggested previously that the explanation may lie, in part, in the adverse effects of angiotensin II on cardiac vagal control [3]. Large trials have shown that impaired cardiac autonomic function is associated with an adverse prognosis in patients with heart failure and after myocardial infarction [4,5].…”

Use of opposing reflex stimuli and heart rate variability to examine the effects of lipophilic and hydrophilic β-blockers on human cardiac vagal control

“…The following time domain measures of heart rate variability were determined : SDNN (standard deviation of R-R interval values), RMSSD (root-mean-square of successive R-R interval differences) and pNN50 (percentage of successive R-R interval differences exceeding 50 ms). In addition, we determined the interquartile differences (75th-25th percentile) of the frequency distributions of the total number of R-R intervals (IQDNN) and of successive R-R interval differences (IQDSD) [19,20].…”

The angiotensin-converting enzyme gene I/D polymorphism and heart rate variability following acute myocardial infarction

“…s Key words Polymorphism · renin-angiotensin system · heart rate variability of AII infusion on high frequency measures of HRV mediated by the vagus [4]. Plasma A II concentration is dependent not only upon the stimulus of renin production but on the activity of angiotensin-converting enzyme (ACE).…”