Biomedical subjects

Jacques W M Lenders

Publications and source records attributed to Jacques W M Lenders.

At least 19 recordsLinked to original sources

PubMed2007

Clinical presentations, biochemical phenotypes, and genotype-phenotype correlations in patients with succinate dehydrogenase subunit B-associated pheochromocytomas and paragangliomas.

CONTEXT: Mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to malignant paraganglioma (PGL). Recognition of the SDHB phenotype in apparently sporadic PGL directs appropriate treatment and family screening. OBJECTIVE: The objective of the study was to assess mutation-specific clinical and biochemical characteristics of SDHB-related PGL. DESIGN: The study design was retrospective descriptive. PATIENTS: PATIENTS included 29 patients (16 males) with SDHB-related abdominal or thoracic PGL. INTERVENTION: There was no intervention. MAIN OUTCOME MEASURES: Clinical presentations, plasma and urine concentrations of catecholamines and O-methylated metabolites, and genotype-phenotype correlations were measured. RESULTS: Mean +/- sd age at diagnosis was 33.7 +/- 15.7 yr. Tumor-related pain was among the presenting symptoms in 54% of patients and was the sole symptom in 14%. Seventy-six percent had hypertension, and 90% lacked a family history of PGL. All primary tumors but one originated from extraadrenal locations. Mean +/- sd tumor size was 7.8 +/- 3.7 cm. In this referral-based study, 28% presented with metastatic disease and all but one eventually developed metastases after 2.7 +/- 4.1 yr. Ten percent had additional head and neck PGLs. The biochemical phenotype was consistent with hypersecretion of both norepinephrine and dopamine in 46%, norepinephrine only in 41%, and dopamine only in 3%. Ten percent had normal catecholamine (metabolite) levels, consistent with biochemically silent PGL. No obvious genotype-phenotype correlations were identified. CONCLUSIONS: SDHB-related PGL often presents as apparently sporadic PGL with symptoms related to tumor mass effect rather than to catecholamine excess. The predominant biochemical phenotype consists of hypersecretion of norepinephrine and/or dopamine, whereas 10% of tumors are biochemically silent. The clinical expression of these tumors cannot be predicted by the genotype.

Adolescent↗

PubMed2007

Is supine rest necessary before blood sampling for plasma metanephrines?

BACKGROUND: The impact of blood sampling in sitting vs supine positions on measurements of plasma metanephrines for diagnosis of pheochromocytoma is unknown. METHODS: We compared plasma concentrations of free metanephrines in samples from patients with primary hypertension obtained after supine rest with those obtained in the sitting position without preceding rest. We also assessed the effects on diagnostic test performance retrospectively in patients with and without pheochromocytoma, and we calculated cost-effectiveness for pheochromocytoma testing. RESULTS: Upper reference limits of plasma free metanephrines were higher in samples obtained from seated patients without preceding rest than from supine patients with preceding rest. Application of these higher upper reference limits to samples from supine patients with pheochromocytoma decreased the diagnostic sensitivity from 99% to 96%. In patients without pheochromocytoma, adjusting the plasma concentration for the effects of sitting while preserving the 99% sensitivity by use of the supine upper reference limits increased the number of false-positive test results from 9% to 25%. CONCLUSIONS: To preserve high diagnostic sensitivity we recommend the use of upper reference limits determined from blood samples collected in the supine position. Under these conditions, negative test results for blood samples obtained with patients sitting are as effective for ruling out pheochromocytoma as negative results from samples obtained after supine rest. Repeat testing with samples obtained in the supine position offers a cost-effective approach for dealing with the increased numbers of false-positive results expected after initial sampling in the sitting position.

Adrenal Gland Neoplasms↗

PubMed2006

Stability of urinary fractionated metanephrines and catecholamines during collection, shipment, and storage of samples.

BACKGROUND: Measurements of 24-h fractionated urinary metanephrines and catecholamines are used for the diagnosis of pheochromocytoma, but adequate information is needed regarding collection, storage, and shipment conditions. METHODS: Spot urine samples were collected from 8 healthy volunteers. Aliquots were immediately frozen at -20 degrees C, or acidified to pH 4 and then frozen either directly or after 24 h at room temperature. The remaining urine was left at room temperature for 24 h and then split into one portion that was acidified and one portion that was not. Aliquots were either frozen or allowed to stand at room temperature for an additional 24, 48, 72, 96, and 168 h before freezing. We also tested the efficacy of adding Na(2)EDTA and Na(2)S(2)O(5), as an alternative to acidification for preservation of the catecholamines. RESULTS: No clinically relevant degradation (<5%) was observed for the fractionated metanephrines under any of the storage conditions. In contrast, in approximately 50% of the untreated samples catecholamines were partially degraded during the first 24 h at room temperature. Immediate acidification, however, prevented degradation, whereas acidification after 24 h prevented further decay. Addition of Na(2)EDTA and Na(2)S(2)O(5) fully prevented degradation of catecholamines during the first 24 h in 4 of 5 cases. In the remaining case, degradation did not exceed 10%. CONCLUSION: Preservation of samples for measurements of urinary fractionated metanephrines is not necessary if samples are assayed or frozen within 1 week, which is an important advantage if transport of samples is necessary. In contrast, urinary catecholamines require preservation measures during collection.

Catecholamines↗

PubMed2006

Transport within the interstitial space, rather than membrane permeability, determines norepinephrine recovery in microdialysis.

Microdialysis is a sampling method that permits measurement of hormones, drugs, and other lower molecular weight compounds present in interstitial fluid. We developed a straightforward mathematical model that predicts a linear relationship between the reciprocal dialysate concentration of the analyte from the interstitium and perfusion rate, permitting estimation of the interstitial concentration by extrapolation to zero perfusion rate. Conversely, linearity between the reciprocal dialysate concentration of internal standard added to the perfusion medium (retrodialysis), and the reciprocal perfusion rate, is predicted. In nine healthy volunteers, interstitial norepinephrine (NE) was estimated by NE measurements in microdialysates obtained from skeletal muscle and adipose subcutaneous tissue, using sodium salicylate (Sal) in the perfusion buffer as internal standard, at perfusion rates of 2 and 5 mul/min. Comparison with microdialysis in vitro by immersing the probe in a large volume of buffer containing NE showed that the in vivo (retro)recovery of NE and Sal is almost exclusively determined by transport of NE through the interstitial space toward and Sal from the membrane and that membrane permeability itself plays a negligible role. This was supported by the observation that applying lower body negative pressure, a measure that is unlikely to affect membrane permeability, resulted in a significant (p < 0.05) decrease of Sal retrorecovery from muscle interstitium. This validated new model significantly adds insight into the factors determining recovery of substances from the interstitium in microdialysis and provides a simpler alternative to previous approaches for estimation of interstitial concentrations.

Adult↗

PubMed2006

Sympathetic nervous system function in HIV-associated adipose redistribution syndrome.

It was recently suggested that HIV-associated adipose redistribution syndrome (HARS) results from an autonomic dysbalance. We investigated the local and global sympathetic nervous system function of patients with HIV-1 infection and HARS. Interstitial noradrenaline concentrations in skeletal muscle and subcutaneous adipose tissue were increased in the absence of changes in global sympathetic nerve activity, consistent with locally increased sympathetic activity. This could promote localized lipolysis in subcutaneous adipose tissue and contribute to the development of HARS.

Adipose Tissue↗

PubMed2006

Emergencies caused by pheochromocytoma, neuroblastoma, or ganglioneuroma.

Pheochromocytoma may lead to important emergency situations, ranging from cardiovascular emergencies to acute abdomen and multiorgan failure. It is vital to think about this disease in any emergency situation when conventional therapy fails to achieve control or symptoms occur that do not fit the initial diagnosis. The importance of keeping this diagnosis in minds is underscored by the fact that, in 50% of pheochromocytoma patients, the diagnosis is initially overlooked. Two other tumors of the sympathetic nervous system, neuroblastoma and ganglioneuroma, are less commonly associated with emergency conditions. If they occur, they are often linked to catecholamine excess, paraneoplastic phenomena, or local tumor mass effect.

Adrenal Gland Neoplasms↗

PubMed2006

The optimal scheme of self blood pressure measurement as determined from ambulatory blood pressure recordings.

OBJECTIVE: To determine how many self-measurements of blood pressure (BP) should be taken at home in order to obtain a reliable estimate of a patient's BP. DESIGN: Participants performed self blood pressure measurement (SBPM) for 7 days (triplicate morning and evening readings). In all of them, office blood pressure (three consecutive readings) and 24-h ambulatory blood pressure were obtained as well. Average SBPM values, obtained from several combinations of readings, were correlated with the results of ambulatory blood pressure measurement (ABPM). In addition, we assessed whether certain patient characteristics would influence such correlations. SETTING: Patients were recruited at hospital or general practice. PATIENTS: A total of 216 untreated hypertensive patients. RESULTS: The average SBPM value calculated from day 3 to day 7, omitting the first measurement of each morning and evening session, gave the best correlation with 24-h ABPM (r = 0.70). However, similar results were obtained from a SBPM value averaged from day 3 until 5 without the first measurement of each triplicate session. Overall, younger patients had significantly better correlations than older ones. Women had significantly better correlations with ABPM than men for systolic morning and daytime SBPM, whereas men had significantly better correlations for daytime and evening diastolic SBPM (P < 0.001). In addition, all correlations increased with lower systolic office blood pressure measurement (OBPM) values. CONCLUSIONS: A minimum number of 5 days of measurement is recommended to obtain a reliable estimate of a patient's usual BP. On each day, three consecutive morning and evening measurements should be performed. For calculating the average SBPM, the first 2 days and the first measurement of each triplicate measurements should be discarded. Moreover, patient characteristics may have an impact on the number of necessary self-measurements. However, because adhering to these recommendations will make SBPM a time-consuming procedure, this type of measurement should be performed only when a decision about starting or changing antihypertensive therapy is needed or in the case of special patient groups.

Adult↗

PubMed2006

Prevalence of the white-coat effect at multiple visits before and during treatment.

OBJECTIVE: To investigate the prevalence and persistence of the white-coat effect (WCE) and white-coat hypertension (WCH) on multiple blood pressure measurement occasions in hypertensive patients with and without treatment. DESIGN: Essential hypertensive patients in whom we took office blood pressure measurements (OBPM) at eight visits (three readings per visit) performed self blood pressure measurements (SBPM) for 1 week prior to each visit (42 readings per week) over a period of 1 year. All measurements were performed with the same automatic device (Omron 705CP). In addition, 24-h ambulatory blood pressure monitoring (ABPM) was performed at the start and at the end of the study. At the start, patients did not use any medication but on subsequent visits they were treated on the basis of their SBPM values. WCH was defined as an OBPM-value > or = 140 and/or 90 mmHg and a SBPM or daytime ABPM value < 135/85 mmHg. This definition was used irrespective of treatment. We also determined the prevalence of a substantial WCE (OBPM 20 mmHg systolic or 10 mmHg diastolic higher than SBPM or daytime ABPM). SETTING: Patients were recruited at hospital or general practice. PATIENTS: A total of 163 mild-to-moderate essential hypertensive patients with a mean age of 56 years (56% males). RESULTS: At eight blood pressure (BP) measurement occasions, 75% of all patients had a substantial WCE at least once, while 57% had WCH at least once. One-third of the patients consistently had a substantial WCE and 14% consistently had WCH on three or more occasions The magnitude of the WCE was significantly related to the height of blood pressure in treated but not in untreated patients. CONCLUSION: In some patients, WCH or a substantial WCE occurs consistently on multiple OBPM visits. Especially in untreated patients, the magnitude of the WCE varies widely among individuals. These results support the incorporation of SBPM and/or ABPM into optimal management of hypertension, not only to prevent misdiagnosis in untreated patients but also to determine the need for adjusting antihypertensive therapy in treated subjects.

Blood Pressure↗

PubMed2006

The position of the arm during blood pressure measurement in sitting position.

OBJECTIVE: Determining the influence of the position of the arm on blood pressure measurement in the sitting position. METHODS: Blood pressure of 128 individuals (the majority being treated hypertensive patients) visiting the outpatient clinic was measured simultaneously on both arms with arms in two different positions. First, both arms were placed at the chair support level and blood pressure was measured three times on both arms after 10 min of rest. Subsequently, while still remaining in the same sitting position, five blood pressure measurements were made simultaneously at both arms with one arm placed on the desk and one arm placed and supported at heart level (mid-sternal). The arm placed at heart level served as the reference arm. The choice of which arm was placed at desk level and which arm was placed at heart level was randomized. RESULTS: Both at desk level and at chair support level, mean (+/-SD) systolic and diastolic blood pressures were higher than blood pressure at heart level by 6.1/5.7+/-4.6/3.1 and 9.3/9.4+/-5.4/3.4 mmHg, respectively. The effect of the height differences between the arm positions on the blood pressure readings was smaller than predicted (0.49 mmHg/cm systolic and 0.47 mmHg/cm diastolic). No significant correlation was found between blood pressure difference in the different arm positions (desk and heart level) and age, sex, weight or baseline blood pressure. CONCLUSIONS: Different arm positions below heart level have significant effects on blood pressure readings. The leading guidelines about arm position during blood pressure measurement are not in accordance with the arm position used in the Framingham study, the most frequently used study for risk estimations.

Adult↗

PubMed2006

Biochemical diagnosis and localization of pheochromocytoma: can we reach a consensus?

Pheochromocytomas can have a highly variable presentation, making diagnosis challenging. To think of the tumor represents the crucial initial step, but establishing the diagnosis requires biochemical evidence of excessive catecholamine production and imaging studies to localize the source. Currently, however, there exist no generally agreed upon guidelines based on which tests and testing algorithms should be used to confirm and locate or exclude a suspected pheochromocytoma. Choice of biochemical tests and imaging studies instead usually depends on institutional experience. At the First International Symposium on Pheochromocytoma (ISP2005), held in Bethesda in October 2005, a panel of experts and patient representatives discussed current problems and available options for tumor diagnosis and localization and formulated recommendations, which were subsequently agreed upon by those in attendance at the meeting. This article summarizes the discussion and recommendations derived from that session.

Adrenal Gland Neoplasms↗

PubMed2006

Gene expression profiling of benign and malignant pheochromocytoma.

There are currently no reliable diagnostic and prognostic markers or effective treatments for malignant pheochromocytoma. This study used oligonucleotide microarrays to examine gene expression profiles in pheochromocytomas from 90 patients, including 20 with malignant tumors, the latter including metastases and primary tumors from which metastases developed. Other subgroups of tumors included those defined by tissue norepinephrine compared to epinephrine contents (i.e., noradrenergic versus adrenergic phenotypes), adrenal versus extra-adrenal locations, and presence of germline mutations of genes predisposing to the tumor. Correcting for the confounding influence of noradrenergic versus adrenergic catecholamine phenotype by the analysis of variance revealed a larger and more accurate number of genes that discriminated benign from malignant pheochromocytomas than when the confounding influence of catecholamine phenotype was not considered. Seventy percent of these genes were underexpressed in malignant compared to benign tumors. Similarly, 89% of genes were underexpressed in malignant primary tumors compared to benign tumors, suggesting that malignant potential is largely characterized by a less-differentiated pattern of gene expression. The present database of differentially expressed genes provides a unique resource for mapping the pathways leading to malignancy and for establishing new targets for treatment and diagnostic and prognostic markers of malignant disease. The database may also be useful for examining mechanisms of tumorigenesis and genotype-phenotype relationships. Further progress on the basis of this database can be made from follow-up confirmatory studies, application of bioinformatics approaches for data mining and pathway analyses, testing in pheochromocytoma cell culture and animal model systems, and retrospective and prospective studies of diagnostic markers.

Adrenal Gland Neoplasms↗

PubMed2005

Pheochromocytoma catecholamine phenotypes and prediction of tumor size and location by use of plasma free metanephrines.

BACKGROUND: Measurements of plasma free metanephrines (normetanephrine and metanephrine) provide a useful test for diagnosis of pheochromocytoma and may provide other information about the nature of these tumors. METHODS: We examined relationships of tumor size, location, and catecholamine content with plasma and urinary metanephrines or catecholamines in 275 patients with pheochromocytoma. We then prospectively examined whether measurements of plasma free metanephrines could predict tumor size and location in an additional 16 patients. RESULTS: Relative proportions of epinephrine and norepinephrine in tumor tissue were closely matched by relative increases of plasma or urinary metanephrine and normetanephrine, but not by epinephrine and norepinephrine. Tumor diameter showed strong positive relationships with summed plasma concentrations or urinary outputs of metanephrine and normetanephrine (r = 0.81 and 0.77; P <0.001), whereas relationships with plasma or urinary catecholamines were weaker (r = 0.41 and 0.44). All tumors in which increases in plasma metanephrine were >15% of the combined increases of normetanephrine and metanephrine either had adrenal locations or appeared to be recurrences of previously resected adrenal tumors. Measurements of plasma free metanephrines predicted tumor diameter to within a mean of 30% of actual diameter, and high plasma concentrations of free metanephrine relative to normetanephrine accurately predicted adrenal locations. CONCLUSIONS: Measurements of plasma free metanephrines not only provide information about the likely presence or absence of a pheochromocytoma, but when a tumor is present, can also help predict tumor size and location. This additional information may be useful for clinical decision-making during tumor localization procedures.

Adrenal Gland Neoplasms↗

PubMed2005

Side effects of ambulatory blood pressure monitoring.

OBJECTIVE: To study the experiences and complaints of patients who underwent 24 h blood pressure monitoring. METHODS: Two groups of hypertensive patients of a tertiary outpatient clinic were asked to fill in a nine-item questionnaire about the side effects of ambulatory blood pressure monitoring (ABPM). The first group (n=75) used the auscultatory Oxford Medilog device (OM) and the second group (n=110) the oscillometric Spacelabs 90207 (SL). RESULTS: The OM showed significantly less error readings (OM versus SL, 9 versus 19%; P=0.005) but was also less tolerated by the subjects. Sleep disturbance was noted in 53% of the OM patients group in comparison with 18% in the SL group (P<0.0001). Adjustment of daily activities occurred more often in the OM group (OM versus SL, 37 versus 19%; P=0.013) as did complaints of pain in the cuffed arm (OM versus SL, 31 versus 11 %; P=0.007). There was no difference in the proportion of patients that refused a second ABPM (OM versus SL, 11 versus 10%). Linear regression analyses showed that differences in side effects between the two devices were not due to differences in blood pressure, heart rate, age or sex. CONCLUSIONS: This study demonstrates that side effects of ABPM are not negligible and that there are differences between devices.

Activities of Daily Living↗

PubMed2005

Plasma metanephrines in renal failure.

BACKGROUND: Diagnosis of pheochromocytoma in renal failure poses a diagnostic dilemma due to lack of reliability of conventional urinary measurements of catecholamine excess. Measurements of the plasma metanephrines, normetanephrine and metanephrine (the O-methylated metabolites of norepinephrine and epinephrine), provide an alternative diagnostic test. The metanephrines may be measured as free metabolites or after a deconjugation step where measurements reflect mainly sulfate-conjugated metabolites. The influence of renal insufficiency states on these various measurements is unclear. METHODS: Plasma free and deconjugated metanephrines and catecholamines in 17 patients on dialysis with end-stage renal disease and 19 patients with renal insufficiency (creatinine clearance, 5-78 mL/min) were compared with levels in 89 hypertensives, 68 healthy normotensives, and 51 patients with von Hippel-Lindau syndrome. RESULTS: Patients with renal failure had up to two-fold higher plasma concentrations of catecholamines and free metanephrines, and more than 12-fold higher plasma concentrations of deconjugated metanephrines than comparison groups. Plasma free metanephrines and catecholamines were, respectively, within the 95% confidence intervals of reference groups in 75% and 42% of the dialysis patients, and in 74% and 68% of patients with renal insufficiency. In contrast, no dialysis patient and only half the renal insufficiency patients had plasma levels of deconjugated metanephrines within the reference intervals. Plasma levels of deconjugated metanephrines, but not free metanephrines, showed strong inverse relationships with creatinine clearance. CONCLUSION: Plasma concentrations of free metanephrines are relatively independent of renal function and are, therefore, more suitable for diagnosis of pheochromocytoma among patients with renal failure than measurements of deconjugated metanephrines.

Adrenal Gland Neoplasms↗

PubMed2004

Long-term effects of unilateral carotid endarterectomy on arterial baroreflex function.

BACKGROUND AND PURPOSE: Carotid endarterectomy (CE) may be complicated by the clinical syndrome of baroreflex failure. Alterations of baroreflex function may also account for the frequently observed blood pressure lability in the first hours following surgery. We investigated the long-term effects of unilateral CE on baroreflex control of function and blood pressure. METHODS: We investigated 14 patients after unilateral CE (13 m:1 f, 64.8 +/- 6.5 years), 9 patients with a surgically untreated uni-/bilateral carotid stenosis (CS, 7 m:2 f, 57.6 +/- 10.7 years) and 12 healthy controls (HC, 11 m:1 f, 60.9 +/- 7.9 years) by means of Valsalva maneuver, active standing, forced breathing, cold face test, cold pressor test and mental arithmetic. Ambulatory blood pressure level and variability were determined from 24-hour Spacelabs and 5-hour beat-to-beat Portapres recordings. RESULTS: Baroreflex sensitivity (derived from phase IV Valsalva maneuver) was significantly lower in CE (1.53 +/- 0.83 ms/mmHg) than in CS (4.39 +/- 2.27, p = 0.002) and HC (5.34 +/- 3.78, p = 0.003). CE patients exhibited a decreased reflex control of heart rate in response to Valsalva's maneuver and active standing without orthostatic hypotension. Office blood pressure levels before and after endarterectomy were similar, as were ambulatory blood pressure levels in the three groups. Ambulatory blood pressure variability was higher in CE and CS than in HC, but not different between CE and CS. CONCLUSIONS: Unilateral CE causes a long-term impairment of baroreflex function, resulting in an attenuated reflex control of heart rate, but no hypertension or blood pressure lability.

Adult↗

PubMed2004

The role of carotid chemoreceptors in the sympathetic activation by adenosine in humans.

The direct vasodilatory and negative chronotropic effects of adenosine in humans are counterbalanced by a reflex increase in sympathetic nerve traffic. A suggested mechanism for this reflex includes peripheral chemoreceptor activation. We, therefore, assessed the contribution of carotid chemoreceptors to sympatho-excitation by adenosine. Muscle sympathetic nerve activity was recorded during adenosine infusion (140 microg.kg(-1).min(-1) for 5 min) in five patients lacking carotid chemoreceptors after bilateral carotid body tumour resection (one male and four female, mean age 51 +/- 11 years) and in six healthy controls (two male and four female, mean age 50 +/- 7 years). Sympathetic responses to sodium nitroprusside injections were assessed to measure baroreceptor-mediated sympathetic activation. In response to adenosine, controls showed no change in blood pressure, an increase in heart rate (+48.2 +/- 13.2%; P<0.003) and an increase in sympathetic nerve activity (+195 +/- 103%; P<0.022). In contrast, patients showed a decrease in blood pressure (-14.6 +/- 4.9/-17.6 +/- 6.0%; P<0.05), an increase in heart rate (+25.3 +/- 8.4%; P<0.032) and no significant change in sympathetic activity. Adenosine-induced hypotension in individual patients elicited less sympathetic activation than equihypotensive sodium nitroprusside injections. In humans lacking carotid chemoreceptors, adenosine infusion elicits hypotension due to the absence of significant sympatho-excitation. Chemoreceptor activation is essential for counterbalancing the direct vasodilation by adenosine. In addition, blunting of the baroreflex sympathetic response to adenosine-induced hypotension may indicate a direct sympatho-inhibitory effect of adenosine.

Adenosine↗

PubMed2004

Cortisol, 11beta-hydroxysteroid dehydrogenases, and hypertension.

Hypersecretion of cortisol is associated with hypertension. In addition, an abnormal cortisol metabolism may play a role in the pathogenesis of hypertension. The 11beta-hydroxysteroid dehydrogenase (11beta-HSD) isozymes catalyze interconversion of cortisol and cortisone and play an important role in the regulation of the effects of cortisol. Activity of 11beta-HSD type 2, converting active cortisol in inactive cortisone, is crucial in preventing access of cortisol to the renal mineralocorticoid receptors (MRs). Decreased activity of this isozyme in the kidney, either congenitally in Apparent Mineralocorticoid Excess syndrome or acquired following licorice consumption, allows cortisol access to the MRs, resulting in hypokalemic hypertension. In normotensive subjects, an association has been demonstrated between blood pressure increase on a high-salt diet and a mild decrease of renal 11beta-HSD2 activity. In ectopic adrenocorticotropic hormone (ACTH), plasma cortisol levels are very high, resulting in mineralocorticoid hypertension caused by saturation of the available renal 11beta-HSD2 capacity. Activity of the 11beta-HSDs has also been demonstrated in many extrarenal sites. Several studies have demonstrated extrarenal effects of cortisol on blood pressure, as well as a possible role for altered extrarenal 11beta-HSD activities in the pathogenesis of hypertension. More studies are needed to clarify the role of 11beta-HSDs in the pathogenesis of hypertension.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2004

Cardiovascular responses to stress after carotid baroreceptor denervation in humans.

Iatrogenic bilateral denervation of carotid sinus baroreceptors may occur as a complication of carotid body tumor resection and radiation therapy of the neck. The acute phase of the resulting syndrome of baroreflex failure is characterized by a limited blood pressure buffering capacity against excessive rise or fall in response to emotional and physical stimuli like sexual arousal and cold. Paroxysms of severe hypertension and tachycardia, accompanied by excessive increments in sympathetic tone and catecholamine plasma levels, were ascribed to loss of tonic inhibitory influence of baroreceptors on sympathetic tone. Bilateral anesthetic blockade of baroreceptor afferent nerves was shown to result in a strong increase in muscle sympathetic nerve activity and disruption of its normal patterning. This chapter reviews our findings on the long-term effects of iatrogenic baroreflex trauma on the hemodynamic responses to pharmacological, physical, and emotional stress in the autonomic function laboratory as well as under daily life conditions. Chronic attenuation of baroreflex sensitivity after carotid body tumor resection and neck irradiation results in an increased blood pressure variability. However, unopposed sympathetic activation in response to physical and emotional stress appears to be limited to the acute phase of baroreflex failure.

Carotid Arteries↗