Effect of chronic angiotensin converting enzyme inhibition on sympathetic nerve traffic and baroreflex control of the circulation in essential hypertension
Abstract
BACKGROUND: Human studies have shown that the blood pressure lowering effects of angiotensin converting enzyme inhibitors are accompanied by a reduction in plasma norepinephrine levels. Whether this is due to central or peripheral mechanisms is unknown, however. OBJECTIVE: To evaluate the effects of chronic interference with the renin-angiotensin system on sympathetic nerve traffic and baroreflex control of vagal and adrenergic cardiovascular drive. PATIENTS AND METHODS: In 18 untreated mild to moderate essential hypertensive patients aged 48.5+/-1.9 years (mean+/-SEM), we measured mean arterial pressure (Finapres), heart rate (electrocardiogram), plasma renin activity (radioimmunoassay), plasma norepinephrine (high-performance liquid chromatography) and postganglionic muscle sympathetic nerve activity (microneurography at a peroneal nerve). In nine patients, measurements were performed before and after 2 months of oral administration of lisinopril (10 mg/day), while in the remaining nine patients they were performed before and after a 2 month observation period, without the drug administration. Measurements were performed at rest and during baroreflex stimulation and deactivation elicited by stepwise intravenous infusions of phenylephrine and nitroprusside, respectively. RESULTS: Lisinopril induced a marked increase in plasma renin activity (from 1.1+/-0.2 to 6.4+/-1.3 ng/ml per h, P< 0.01) and a reduction in mean arterial pressure (from 109.6+/-3.1 to 98.7+/-2.9 mmHg, P < 0.01) without affecting the heart rate. Plasma norepinephrine and muscle sympathetic nerve activity values were not significantly different before and after lisinopril treatment (plasma norepinephrine values changed from 290.4+/-39.2 to 308.1+/-67.1 pg/ml; muscle sympathetic nerve activity changed from 56.4+/-5.3 to 50.6+/-6.6 bursts/100 heart beats). Neither the sympathoinhibitory nor the sympathoexcitatory responses to phenylephrine and nitroprusside were affected by lisinopril, nor the concomitant bradycardia and tachycardia. The curves relating mean arterial pressure to heart rate and muscle sympathetic nerve activity values during baroreceptor manipulation were shifted to the left, indicating a resetting of the baroreflex to the lower blood pressure values achieved during treatment. CONCLUSIONS In essential hypertension, sympathetic nerve traffic is not affected by chronic angiotensin converting enzyme inhibitor treatment that effectively interferes with the renin-angiotensin system and lowers the elevated blood pressure. The baroreflex ability to modulate heart rate and central sympathetic outflow is also unaffected. These data argue against the existence of a central sympathoexcitatory effect of angiotensin II in this condition. They also indicate that antihypertensive treatment with an angiotensin converting enzyme inhibitor preserves autonomic reflex control, with favorable consequences for cardiovascular homeostasis.
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The increased sympathetic activity in EHT+LVH was not attributable to antihypertensive treatment.
“Therefore, the increased activity in EHT + LVH was not attributable to antihypertensive treatment and, in fact, was still apparent despite the use of agents”
From Hypertensive left ventricular hypertrophy: relation to peripheral sympathetic drive (2001) · cites this paper as [31]
Treatment with angiotensin-converting enzyme inhibitors in hypertension has been shown to have either no effect or decrease sympathetic nerve traffic.
“Also, treatment with angiotensin-converting enzyme inhibitors in hypertension has been shown to have either no effect or decrease sympathetic nerve traffic (31,32).”
From Hypertensive left ventricular hypertrophy: relation to peripheral sympathetic drive (2001) · cites this paper as [31]
Although an effect of medications in the two hypertensive groups cannot be completely excluded, they could not have entirely caused the excessive sympathetic hyperactivity.
“Therefore, although we cannot completely exclude an effect of medications in our 2 hypertensive groups, they could not have entirely caused the excessive sympathetic hyperactivity.”
From Sympathetic Neural Activation in Nondiabetic Metabolic Syndrome and Its Further Augmentation by Hypertension (2004) · cites this paper as [22]
Chronic ACE inhibitor therapy does not affect MSNA levels in hypertensive patients.
“Although we cannot entirely exclude some influence of these agents, it is known in hypertensive patients that chronic ACE inhibitor therapy does not affect MSNA levels, 22 ARBs may decrease it, 23 and -blockers may have no effect or decrease MSNA.24,25”
From Sympathetic Neural Activation in Nondiabetic Metabolic Syndrome and Its Further Augmentation by Hypertension (2004) · cites this paper as [22]
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- Authors
- Grassi, G., Turri, C., DellʼOro, R., Stella, M. L., Bolla, G. B., & Mancia, G.
- Affiliations
- University of Milan (IT)
- Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico (IT)
- Corresponding author
- Mancia, Giuseppe
- Venue
- Journal of Hypertension
- Published
- 1998-12
- Volume
- 16
- Issue
- 12
- Pages
- 1789-1796
- ISSN
- 0263-6352 (ISSN-L)
- OpenAlex
- W1973322174
- Cited by
- 77
- References
- 33
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 1 · 2022: 1 · 2021: 1 · 2018: 3 · 2017: 1 · 2016: 2 · 2015: 1 · 2014: 5 · 2013: 3 · 2012: 1
- FWCI
- 2.63
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- essential hypertension, ACE inhibitors, lisinopril, renin-angiotensin system, baroreflex control, muscle sympathetic nerve activity, plasma norepinephrine, plasma renin activity, baroreflex sensitivity, phenylephrine, sodium nitroprusside, blood pressure
- MeSH terms
- Administration, Oral, Angiotensin-Converting Enzyme Inhibitors, Blood Circulation, Humans, Hypertension, Male, Middle Aged, Sympathetic Nervous System, Baroreflex, Lisinopril
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