Diminished baroreceptor sensitivity in elderly hypertensives Possible role of atherosclerosis

doi:10.1016/0021-9150(76)90079-4

Atherosclerosis

Volume 24, Issues 1–2, July–August 1976, Pages 243-249

https://doi.org/10.1016/0021-9150(76)90079-4 Get rights and content

Abstract

Baroreceptor sensitivity was studied in twelve young normotensive subjects and forty hypertensive patients, separated into two groups according to their age, severity of hypertension and signs of severe atherosclerotic vascular disease. Under stabilized circulatory conditions, the changes of pulse rate in response to changes of blood pressure, attained by infusion of trimethaphan camphorsulfonate alone or with norepinephrine, was examined. There was gradually diminished change of pulse rate in relationship to blood pressure change as age and hypertension advanced. However, although the blood pressure threshold of stimulation was obviously higher in the middle-aged hypertensive subjects than in the normotensive ones, the slightly reduced baroreceptor sensitivity was not significantly different from that in the normotensive group. Only in the elderly hypertensive patients was significantly diminished baroreceptor sensitivity demonstrated, which was also significantly different from that in the middle-aged hypertensive patients. It is speculated that the significantly diminished baroreceptor sensitivity found in the elderly hypertensive patients may be due to atherosclerotic changes in the region of the baroreceptors, although proof of that is not available at the present time.

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Cited by (43)

Essential hypertension - Is erroneous receptor output to blame?
2012, Medical Hypotheses
Citation Excerpt :
Erroneous output form baroreceptors could be caused by both mechanical and biochemical factors affecting either an arterial wall or baroreceptor nerve endings. Arteriosclerosis has been found to decrease the sensitivity of baroreceptors and baroreflex in animals [28,29] and humans [30,31]. Stiffer blood vessels are one of the possible explanations for the dysfunction of baroreceptors.
Hypertension is a chronic medical condition in which systemic arterial blood pressure is elevated. About 80–90% of diagnosed hypertension is considered essential (idiopathic), which means there is no obvious cause of the increase in blood pressure. My hypothesis states that part of idiopathic hypertension results from erroneous information that the brain receives from receptors involved in the regulation of arterial blood pressure, i.e. if, despite high systemic blood pressure, the brain receives false “low-arterial pressure input” from cardiovascular receptors. As a result the brain centres which control blood pressure reset and produce an inappropriate output to the effectors (heart, blood vessels, kidneys and glands). The information errors may result from: (i) structural and/or functional impairment of cardiovascular receptors, (ii) changes in cardiovascular receptors activity, which are caused by other factors than changes in blood pressure, and (iii) impaired transmission in afferent fibres. I assume that in contrast to the lack of input from damaged or denervated cardiovascular receptors, an erroneous input will impair the control of arterial blood pressure. This will apply especially to false input which imitates “low-arterial pressure input”. Higher priority of “low-arterial pressure input” over “high-arterial pressure input” or none input may be explained by the evolutionary adaptation, i.e. low blood pressure, mostly due to haemorrhage, used to be a more common condition than high blood pressure and constitute a major threat to humans.
Carotid barochemoreceptor pathological findings regarding carotid plaque status and aging
2009, Canadian Journal of Cardiology
Carotid barochemoreceptor pathological lesions have been studied in animals, but few human necropsies have been performed. Therefore, data rely on case patients following surgery, radiotherapy and carotid endarterectomy. Almost no data are available regarding whether the effect of aging prevails over pathological conditions, despite the classic description that glomic fibrosis increases with age.
To morphometrically characterize the alterations of the carotid barochemoreceptors and their supplying arteries.
Patients (n = 23) who had suffered and died from stroke, with and without complicated internal carotid atheromatosis, were divided by age (group 1: older than 80 years; group 2: 65 to 80 years; and group 3: younger than 65 years). Carotid segments were obtained at autopsy. The specimens were stained for light microscopy and immunohistochemistry.
Carotid glomus presented from moderate-to-severe atrophy and fibrosis. A focal decrease in vascularization (CD34-positive) of the glomus (greater than 50%) was observed in areas of atrophy and fibrosis. Damaged nerve endings (S100 protein-positive) were observed at the media of the carotid sinus. Morphometric data showed no differences between groups for glomus area, number of type 1 and 2 cells, and the wall to lumen arteriole ratio. No statistical differences were demonstrated in the pathological findings of the carotid glomus when comparing complicated with noncomplicated plaques or age groups.
Severe carotid chemoreceptor damage exists in patients who have died from stroke and suffered from carotid atheromatosis. These findings were independent from aging and plaque type. However, damage was correlated with a marked narrowing of the supplying arterioles as a consequence of hemodynamic and/or metabolic alterations (dyslipidemia, diabetes).
Les anomalies anatomopathologiques touchant les barorécepteurs et les chimiorécepteurs carotidiens ont fait l’objet d’études chez l’animal, mais on dispose de peu de données anatomopathologiques chez l’être humain. Les données disponibles proviennent de spécimens prélevés chez des patients qui ont subi une chirurgie, des traitements de radiothérapie ou une endartériectomie carotidienne. On ne dispose pour ainsi dire d’aucune donnée pour vérifier si l’effet du vieillissement supplante celui d’autres pathologies, malgré la description classique de l’aggravation de la fibrose glomique avec l’âge.
Recenser les altérations morphométriques des baro- et chimiorécepteurs et des artères qui les irriguent.
Des patients (n = 23) décédés des suites d’un accident vasculaire cérébral (AVC), atteints ou non d’athéromatose carotidienne interne compliquée, ont été répartis selon l’âge (groupe 1 : 80 ans et plus; groupe 2 : de 65 à 80 ans et groupe 3, moins de 65 ans). Les segments de carotides ont été prélevés à l’autopsie. Les spécimens ont été colorés pour examen microscopique et analyse immunohistochimique.
Le glomus carotidien présentait une atrophie et une fibrose de modérées à graves. Les auteurs ont noté une diminution en foyers (CD34-positive) de la vascularisation du glomus (plus de 50 %) dans les zones d’atrophie et de fibrose. Ils ont observé une atteinte (protéine S100-positive) des terminaisons nerveuses au niveau de la média du sinus carotidien. Les données morphométriques n’ont montré aucune différence entre les groupes pour ce qui est de l’aire du glomus, du nombre de cellules de types 1 et 2 et du rapport paroi-lumière artériolaires. Les auteurs n’ont observé aucune différence statistique entre les anomalies du glomus carotidien lorsqu’ils ont comparé les groupes d’âge ou les plaques compliquées et non compliquées.
On note de graves anomalies des chimiorécepteurs chez les patients qui sont décédés des suite d’un AVC et qui souffraient d’athéromatose carotidienne. Ces observations étaient indépendantes de l’âge et du type de plaque. Toutefois, les atteintes étaient en corrélation avec un rétrécissement marqué de la lumière des artérioles en cause, consécutif à des anomalies hémodynamiques et/ou métaboliques (dyslipidémie, diabète).
Abnormalities of cardiac autonomic nervous activity correlate with expansive coronary artery remodeling
2008, Atherosclerosis
Citation Excerpt :
Angell-James described a reduced afferent baroreceptor activity in atherosclerotic animals [19]. Vlachakis et al. proposed that atherosclerosis contributes to autonomic dysfunction in elder hypertensive patients [20]. Receptor nerve endings terminate in the vascular adventitia [10].
Vagal fibres are distributed both in the perivascular connective tissue and in the adventitia around the circumference of arteries, and contribute to coronary artery dilation. The aim of the manuscript is to examine whether morphologic changes of the vessel wall due to the atherosclerotic process might be associated with autonomic nervous system dysfunction.
We studied 42 patients with single vessel disease referred for percutaneous coronary revascularization. Patients underwent intravascular ultrasound at the site of the ischemia-related artery before intervention. The autonomic nervous system activity was assessed by the analysis of heart rate variability (HRV) in the frequency domain. The high frequencies (HF) are predominantly under the influence of the parasympathetic system, while the low/high frequency (LF/HF) ratio represents an index of sympatho-vagal balance. Plaque plus media cross-sectional area was inversely related to HF components (r = −0.34, p < 0.05), and directly related to LF/HF ratio (r = 0.38, p < 0.05). Patients with expansive remodeling showed lower HF values (0.07 ± 0.06 nu versus 0.14 ± 0.09 nu, p < 0.01) and higher LH/HF ratio (2.1 ± 1.1 versus 1.4 ± 1.1; p < 0.05). LF changes were independent of any morphologic features. On multivariate analyses the remodeling index was the only independent determinant of HF and LF/HF ratio.
Outward stretch of the vessel wall behind the plaque, as a consequence of increasing plaque size and expansive arterial remodeling is associated to autonomic dysfunction namely due to impairment of the vagal tone. It is unknown if remodeling is a cause of vagal impairment or if vagal impairment may contribute to arterial remodeling.
Effects of ACE Inhibition and β-Blockade on Plasminogen Activator Inhibitor-1 and Transforming Growth Factor-β<inf>1</inf> in Carotid Glomus and Autonomic Ganglia in Hypertensive Rats
2007, American Journal of Hypertension
Citation Excerpt :
After observing our results in this study, undoubtedly, the emergent question should be what is the clinical importance and projection of these data? A possible answer could be based on the information suggesting that the baroreflex attenuation in humans might be a consequence of atherosclerotic or hypertensive processes.29,30 Furthermore, a fibrotic appearance of the CG has been demonstrated in elderly patients, suggesting an arteriolar involvement leading to fibrosis by a chronic hypoxic mechanism.31
Previous studies have demonstrated a high correlation between arterial hypertension and the development of lesions in the carotid glomus (CG) and autonomic ganglia (AG), characterized by extracellular matrix (ECM) expansion and reduction in the number of AG neurons. Because lowering blood pressure (BP) is the first step in controlling the deleterious effects of arterial hypertension, the objective was to evaluate possible differences between the β-blocker atenolol (AT) and the angiotensin-converting enzyme (ACE) inhibitor ramipril (RAM) regarding a protective role on CG and AG, as target organs in the spontaneously hypertensive rat (SHR).
Male 12-week-old SHR and Wistar-Kyoto rats (WKY) were divided into SHR; SHR-RAM, 1 mg/kg/d; SHR-AT, 100 mg/kg/d; and WKY rats. After 6 months, the animals were sacrificed and CG and AG were processed by hematoxylin and eosin (H&E) and Masson’s trichrome and immunohistochemistry (transforming growth factor-β₁ and plasminogen activator inhibitor-1).
At the end of the experiment, SHR-AT and SHR-RAM showed a similar control in BP compared with SHR. However, SHR-RAM presented a significant reduction in ECM expansion in CG, AG, and autonomic nerves. Moreover, the number of neurons in AG was preserved with AT and even more with RAM, when compared with SHR group. Transforming growth factor-β₁ and plasminogen activator inhibitor-1 were increased in CG and AG in SHR and in SHR-AT, whereas SHR-RAM showed a similar expression to the WKY group.
According to these results, RAM but not AT provided a significant protective role against structural changes in CG as well as in AG caused by arterial hypertension in SHR. This effect seems to be independent of BP reduction.
Aspirin restores normal baroreflex function in hypercholesterolemic rats by its antioxidative action
2007, European Journal of Pharmacology
Besides its well-known effects on platelet aggregation, aspirin has been suggested to be an antioxidant and is also known to improve the lipid profile. In the present study we tested the hypothesis that aspirin by its antioxidant effect, improves haemodynamic profile and baroreflex sensitivity in rat model of hypercholesterolemia. Hypercholesterolemia was induced in Wistar rats by feeding 1% cholesterol rich diet for 10 weeks. Lipid profile, lipid peroxidation and reduced glutathione were estimated in serum. Haemodynamic changes and baroreflex were measured in anaesthetized rats. Hypercholesterolemic rats showed significant increase in total cholesterol, low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein-cholesterol (VLDL-C) and atherogenic index and significant decrease in high-density lipoprotein-cholesterol (HDL-C). Significant rise in blood pressure, heart rate and attenuation of baroreflex sensitivity were also found in hypercholesterolemic rat. Aspirin in the dose of 100 mg/kg showed significant decrease in total cholesterol, LDL-C, VLDL-C and atherogenic index and significant increase in HDL-C. Aspirin treatment prevented the rise in blood pressure, heart rate and significantly improved baroreflex sensitivity in hypercholesterolemic rats. Hypercholesterolemic rats showed free radical generation, evident by a significant increase in serum lipid peroxidation and significant reduction in serum reduced glutathione content. Aspirin treatment significantly decreased lipid peroxidation and significantly increased reduced glutathione content. We have demonstrated that aspirin improves baroreflex response and prevents the rise in blood pressure and heart rate possibly by reducing sympathetic activity due to its antioxidant effect in experimentally induced hypercholesterolemic rats.
Arterial baroreflex dysfunction promotes atherosclerosis in rats
2005, Atherosclerosis
The present study was designed to testify the hypothesis that arterial baroreflex dysfunction promotes the development of atherosclerosis. Experiment 1: the baroreflex sensitivity (BRS) was measured in 30 Sprague-Dawley (SD) rats in conscious state with a computerized blood pressure monitoring system. Four weeks later, the rats were administered with Vitamin D₃, and fed with the high-cholesterol diet for 8 weeks to induce atherosclerosis. The hearts and aortae were removed for pathological examination. A negative correlation was found between BRS and the scores of coronary (r = −0.464, P < 0.01) or aortic atherosclerosis (r = −0.524, P < 0.01) in SD rats. Experiment 2: sinoaortic denervation (SAD) was performed in SD rats. Then atherosclerosis was also induced. The atherosclerosis scores in SAD rats were significantly higher than those in sham-operated rats (aortic score: 1.50 ± 0.41 versus 1.10 ± 0.39, P < 0.05; coronary score: 1.70 ± 0.35 versus 1.25 ± 0.54, P < 0.05). Using immunohistochemistry and Western blotting methods, it was found that the expressions of C-reactive protein, intercellular adhesion molecule-1 and vascular-cell adhesion molecule-1 in coronary artery and aorta were increased in SAD rats compared with sham-operated rats. These results indicate that arterial baroreflex dysfunction promotes the development of atherosclerosis in rats, and that inflammation may be involved in this process.

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^∗: The Joe Lowe and Louis Price Professor of Medicine

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Research paperDiminished baroreceptor sensitivity in elderly hypertensives Possible role of atherosclerosis

Abstract

Lancet

Role of the baroreceptor reflex in daily control of arterial blood pressure and other variables in dogs

Circ. Res.

Hemodynamic characteristics of chronic experimental neurogenic hypertension in unanesthetized dogs

Circ. Res.

Low arterial pressure in awake rabbits without carotid sinus and aortic nerves

Aortic baroreceptor activity in single fibres of the aortic nerve of atherosclerotic rabbits

Clin. Sci.

Pathophysiology of aortic baroreceptors in rabbits with vitamin D sclerosis and hypertension

Circ. Res.

The relationship of the carotid sinus mechanism to persistent high blood pressure in man

Clin. Sci.

Diminished baroreflex sensitivity in high blood pressure

Circulation

Effect of age and high blood pressure on baroreflex sensitivity in man

Circ. Res.

Baroreflex sensitivity in patients on long-term hemodialysis

Clin. Sci.

Research paper
Diminished baroreceptor sensitivity in elderly hypertensives Possible role of atherosclerosis