Acute effects of angiotensin-converting enzyme inhibition versus angiotensin II receptor blockade on cardiac sympathetic activity in patients with heart failure

Abstract

The beneficial effects of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II (ANG II) receptor antagonists in patients with heart failure secondary to reduced ejection fraction (HFrEF) are felt to result from prevention of the adverse effects of ANG II on systemic afterload and renal homeostasis. However, ANG II can activate the sympathetic nervous system, and part of the beneficial effects of ACE inhibitors and ANG II antagonists may result from their ability to inhibit such activation. We examined the acute effects of the ACE inhibitor captopril (25 mg, = 9) and the ANG II receptor antagonist losartan (50 mg, = 10) on hemodynamics as well as total body and cardiac norepinephrine spillover in patients with chronic HFrEF. Hemodynamic and neurochemical measurements were made at baseline and at 1, 2, and 4 h after oral dosing. Administration of both drugs caused significant reductions in systemic arterial, cardiac filling, and pulmonary artery pressures ( < 0.05 vs. baseline). There was no significant difference in the magnitude of those hemodynamic effects. Plasma concentrations of ANG II were significantly decreased by captopril and increased by losartan ( < 0.05 vs. baseline for both). Total body sympathetic activity increased in response to both captopril and losartan ( < 0.05 vs. baseline for both); however, there was no change in cardiac sympathetic activity in response to either drug. The results of the present study do not support the hypothesis that the acute inhibition of the renin-angiotensin system has sympathoinhibitory effects in patients with chronic HFrEF.

The renin–angiotensin system in cardiovascular autonomic control: recent developments and clinical implications

“…ARBs produce reflexive increases in plasma renin activity and ineffective Ang II, resulting in increased Ang-(1-7) formation. Some studies have shown neutral effects of ACE inhibitors and ARBs on measures of sympathetic tone such as plasma norepinephrine and muscle sympathetic nerve activity in clinical populations [72,73,37,[74][75][76]. The collective literature, however, suggests that the beneficial effects of these therapies on blood pressure are, at least in part, due to cardiovascular autonomic mechanisms (Table 2) [62].…”

Impact of blood glucose control on sympathetic and vagus nerve functional status in patients with type 2 diabetes mellitus

“…However, due to the complexity of the detection method, MSNA technology is not widely used in the daily clinical setting. With the development of isotope tracing technology, total body and cardiac sympathetic activities could be estimated using the norepinephrine spillover technique [11]. Tritium norepinephrine is injected from peripheral vein for 20 min to stabilize the plasma concentration.…”

“…Tritium norepinephrine is injected from peripheral vein for 20 min to stabilize the plasma concentration. Norepinephrine clearance and spillover rates are calculated according to a formula [11]. This technique was more accurate than catecholamine alone in assessing sympathetic neurotransmitter release.…”

“…Newton et al [12] reported that digoxin reduced cardiac norepinephrine spillover in heart failure patients with elevated filling pressures, suggesting that digoxin could reduce cardiac sympathetic nerve activity in patients with severe heart failure. The measurements could evaluate global sympathetic outflow, but they are not suitable for assessment of heterogonous changes in regional sympathetic outflow [11]. The complexity and difficulty of this method limit its clinic application.…”

Effect of Cardioselective Beta Blocker on Lisinopril Treated Isolated Rabbit’s Heart

“…It was also reported that variations in the sympathetic derive observed in cardiac failure. In these types of observation physician may sometimes prescribe Beta blocker to reduces the cardiac effects of epinephrine [19,20]. Many clinical trials are also conducted to prove the additive role of beta-blockers with ACE inhibitors [21].…”