scholarly journals Pharmacological and Genetic Blockade of Trpm7 in the Carotid Body Treats Obesity-Induced Hypertension

Hypertension ◽  
2021 ◽  
Author(s):  
Mi-Kyung Shin ◽  
Roxana Mitrut ◽  
Chenjuan Gu ◽  
Lenise J. Kim ◽  
Bonnie H.Y. Yeung ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Carotid Body ◽  
Transient Receptor Potential ◽  
Blood Pressure Monitoring ◽  
Cation Channel ◽  
Obese Mice ◽  
Carotid Bodies ◽  
Induced Hypertension

Obesity increases levels of an adipocyte-produced hormone leptin, which activates the sympathetic nervous system leading to hypertension. We have recently reported that acute leptin infusion induces hypertension acting via the TRPM7 (transient receptor potential cation channel subfamily M member 7) cation channel in the carotid bodies. We hypothesize that this mechanism causes hypertension when leptin levels are elevated chronically as observed in diet-induced obesity. We have developed a novel extended release preparation, hydrogel, of a TRPM7 inhibitor FTY720, which was administered to the carotid body area bilaterally and compared with control hydrogel in (1) male lean C57BL/6J mice treated with subcutaneous infusions of leptin; (2) diet-induced obese male C57BL/6J with hyperleptinemia at baseline. In the experiment (3), diet-induced obese C57BL/6J mice, in which Trpm7 was silenced in the carotid body areas by transfection with Ad-Trpm7 shRNA, were compared with control mice transfected with Ad-CON-shRNA . All mice were implanted in the left femoral artery with telemetry before the experiments for continuous blood pressure monitoring. In lean mice, leptin increased 24 hours mean arterial pressure from 101.2±1.2 to 112±1.5 mm Hg; Trpm7 inhibitor abolished leptin-induced hypertension. Obese mice had elevated mean arterial pressure of 115.3±1.7 mm Hg, which was lowered by 8.7±1.0 mm Hg on week 2 after Trpm7 inhibitor treatment ( P <0.001), and this effect persisted by week 3. Trpm7 shRNA decreased blood pressure from 119.0±2.2 to 109.6±1.4 mm Hg ( P <0.01), whereas scrambled shRNA had no effect. In conclusion, our study has shown that inhibition of TRPM7 in carotid bodies abolished leptin-induced hypertension in obese mice.

scholarly journals Mean Arterial Pressure and Chronic Kidney Disease Progression in the CKiD Cohort

Hypertension ◽  
2021 ◽  
Author(s):  
Janis M. Dionne ◽  
Shuai Jiang ◽  
Derek K. Ng ◽  
Joseph T. Flynn ◽  
Mark M. Mitsnefes ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Mean Arterial Pressure ◽  
Kidney Disease ◽  
Arterial Pressure ◽  
Disease Progression ◽  
Ambulatory Blood Pressure ◽  
Blood Pressure Monitoring ◽  
Risk Of Progression ◽  
Kidney Disease Progression

Consensus blood pressure guidelines vary in their recommended ambulatory blood pressure targets for children with chronic kidney disease (CKD) because of limited research in this area. We analyzed longitudinal ambulatory blood pressure monitoring data from 679 children with moderate CKD enrolled in the observational CKiD (Chronic Kidney Disease in Children) cohort by time-varying mean arterial pressure (MAP) percentile categories based on the highest wake or sleep MAP percentile. Analyses were stratified by nonglomerular and glomerular diagnoses, with 3 models constructed: unadjusted, adjusted for age, sex, and race, and additional adjustment for proteinuria. The outcome of interest was time to renal replacement therapy or 50% decline in baseline renal function. We found that among children with nonglomerular CKD, MAP percentile was not associated with accelerated disease progression risk until after 4 years of follow-up at which point a high MAP (>90th percentile) was associated with a higher risk of progression to the composite end point (HR, 1.88 [CI, 1.03–3.44]). Among those with glomerular CKD, differential risk for progression began from baseline with the highest risk in those with MAP >90th percentile (HR, 3.23 [CI, 1.34–7.79]). These relationships were attenuated somewhat after adjustment for level of proteinuria, but the trend for higher MAP being associated with higher risk of progression remained significant. Thus, in children with CKD, having ambulatory wake or sleep MAP >90th percentile was associated with higher risk of kidney disease progression with the highest levels of MAP associated with the greatest risk of progression. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT00327860

scholarly journals Intraoperative Blood Pressure Monitoring in Obese Patients

2020 ◽  
Author(s):  
Roman Schumann ◽  
Agnes S. Meidert ◽  
Iwona Bonney ◽  
Christos Koutentis ◽  
Wilbert Wesselink ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Systolic Blood Pressure ◽  
Diastolic Blood Pressure ◽  
Blood Pressure Monitoring ◽  
Lower Leg ◽  
Obese Patients ◽  
Upper Arm ◽  
Better Than

Background The optimal method for blood pressure monitoring in obese surgical patients remains unknown. Arterial catheters can cause potential complications, and noninvasive oscillometry provides only intermittent values. Finger cuff methods allow continuous noninvasive monitoring. The authors tested the hypothesis that the agreement between finger cuff and intraarterial measurements is better than the agreement between oscillometric and intraarterial measurements. Methods This prospective study compared intraarterial (reference method), finger cuff, and oscillometric (upper arm, forearm, and lower leg) blood pressure measurements in 90 obese patients having bariatric surgery using Bland–Altman analysis, four-quadrant plot and concordance analysis (to assess the ability of monitoring methods to follow blood pressure changes), and error grid analysis (to describe the clinical relevance of measurement differences). Results The difference (mean ± SD) between finger cuff and intraarterial measurements was −1 mmHg (± 11 mmHg) for mean arterial pressure, −7 mmHg (± 14 mmHg) for systolic blood pressure, and 0 mmHg (± 11 mmHg) for diastolic blood pressure. Concordance between changes in finger cuff and intraarterial measurements was 88% (mean arterial pressure), 85% (systolic blood pressure), and 81% (diastolic blood pressure). In error grid analysis comparing finger cuff and intraarterial measurements, the proportions of measurements in risk zones A to E were 77.1%, 21.6%, 0.9%, 0.4%, and 0.0% for mean arterial pressure, respectively, and 89.5%, 9.8%, 0.2%, 0.4%, and 0.2%, respectively, for systolic blood pressure. For mean arterial pressure and diastolic blood pressure, absolute agreement and trending agreement between finger cuff and intraarterial measurements were better than between oscillometric (at each of the three measurement sites) and intraarterial measurements. Forearm performed better than upper arm and lower leg monitoring with regard to absolute agreement and trending agreement with intraarterial monitoring. Conclusions The agreement between finger cuff and intraarterial measurements was better than the agreement between oscillometric and intraarterial measurements for mean arterial pressure and diastolic blood pressure in obese patients during surgery. Forearm oscillometry exhibits better measurement performance than upper arm or lower leg oscillometry. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New

scholarly journals Incidence, Severity, and Detection of Blood Pressure Perturbations after Abdominal Surgery

2019 ◽  
Vol 130 (4) ◽  
pp. 550-559 ◽  
Author(s):  
Alparslan Turan ◽  
Christine Chang ◽  
Barak Cohen ◽  
Wael Saasouh ◽  
Hani Essber ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Abdominal Surgery ◽  
Arterial Pressure ◽  
Vital Sign ◽  
Continuous Monitoring ◽  
Blood Pressure Monitoring ◽  
Kidney Injury ◽  
Noninvasive Monitor ◽  
Pressure Perturbations

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Intraoperative and postoperative hypotension are associated with myocardial and kidney injury and 30-day mortality. Intraoperative blood pressure is measured frequently, but blood pressure on surgical wards is usually measured only every 4 to 6 h, leaving long intervals during which hypotension and hypertension may be undetected. This study evaluated the incidence and severity of postoperative hypotension and hypertension in adults recovering from abdominal surgery and the extent to which serious perturbations were missed by routine vital-sign assessments. Methods Blood pressure was recorded at 1-min intervals during the initial 48 h in adults recovering from abdominal surgery using a continuous noninvasive monitor. Caregivers were blinded to these measurements and depended on routine vital-sign assessments. Hypotension and hypertension were characterized as time under and above various mean arterial pressure thresholds. Results Of 502 available patients, 312 patients with high-quality records were analyzed, with a median measurement time of 48 [interquartile range: 41, 48] postoperative hours. Nearly a quarter experienced an episode of mean arterial pressure of less than 70 mm Hg lasting at least 30 min (24%; 95% CI, 20%, 29%), and 18% had an episode of mean arterial pressure of less than 65 mm Hg lasting at least 15 min. Nearly half the patients who had mean arterial pressure of less than 65 mm Hg for at least 15 min (47%; 95% CI, 34%, 61%) were undetected by routine vital-sign assessments. Episodes of mean arterial pressure greater than 110 mm Hg lasting at least 30 min were observed in 42% (95% CI, 37%, 48%) of patients; 7% had mean arterial pressure greater than 130 mm Hg for at least 30 min, 96% of which were missed by routine assessments. Episodes of mean arterial pressure less than 65 mm Hg and mean arterial pressure greater than 110 mm Hg captured by routine vital-sign assessments but not by continuous monitoring occurred in 34 and 8 patients, respectively. Conclusions Postoperative hypotension and hypertension were common, prolonged, profound, and largely undetected by routine vital-sign assessments in a cohort of adults recovering from abdominal surgery. Frequent or continuous blood pressure monitoring may detect hemodynamic perturbations more effectively and potentially facilitate treatment.

Haemodynamics of Acth-Induced Hypertension in Sheep

1979 ◽  
Vol 57 (s5) ◽  
pp. 333s-336s ◽  
Author(s):  
B. A. Scoggins ◽  
K. J. F. Allen ◽  
J. P. Coghlan ◽  
D. A. Denton ◽  
W. F. Graham ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cardiac Output ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Adrenocorticotropic Hormone ◽  
Cardiac Rate ◽  
Blood Concentrations ◽  
Acth Treatment ◽  
Induced Hypertension

1. Administration of adrenocorticotropic hormone (ACTH) to sheep produced increases in mean arterial pressure within 24 h associated with an increase in cardiac output and cardiac rate. Both cardiac output and blood pressure remained elevated over the 5 days of ACTH treatment. 2. Administration of ACTH during β-adrenoreceptor blockade resulted in an increase in blood pressure without changes in cardiac output at 24 h. 3. Administration of a combined steroid infusion over 5 days produced increases in cardiac output identical with the effects of ACTH but with a substantially smaller effect on blood pressure. 4. These data suggest that the observed changes in cardiac output produced by ACTH treatment may be associated with high blood concentrations of adrenocortical steroids rather than being necessary for the development of the hypertension.

PATTERN OF MEAN ARTERIAL PRESSURE DURING THE COURSE OF PREGNANCY

2021 ◽  
pp. 70-71
Author(s):  
A. Kala
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Urban Population ◽  
Sedentary Lifestyle ◽  
Pregnancy Induced Hypertension ◽  
Serial Measurement ◽  
Induced Hypertension ◽  
Increasing Trend ◽  
Duration Of Pregnancy

Background and Objectives: The incidence of Pregnancy Induced Hypertension is in increasing trend nowadays due to sedentary lifestyle during pregnancy and also due to various other factors. The aim of this study is to measure the incidence of PIH in a semi urban population of Tirunelveli town and to know the correlation between failure of a mid-trimester dip in mean arterial pressure and development of PIH later in pregnancy by serial measurement of blood pressure starting from rst trimester until delivery of the baby. Main objective is to nd out whether failure of mid trimester fall in blood pressure can be used as a predictor for development of PIH. Materials and Methods: About 100 pregnant women in their early pregnancy i.e. 6 to 7 weeks pregnancy were selected from semi urban population of Tirunelveli town. These women were selected while attending Kandiaperi Government Hospital which is located in Tirunelveli town. Serial measurement of blood pressure done using standard sphygmomanometer once in every two weeks until delivery and mean arterial pressure calculated. Pattern of mean arterial pressure noted in every visit, incidence of PIH noted and correlation between failure of dip in MAP in mid trimester and development of PIH analyzed. Incidence of PIH was 5%. Dip in Results: mean arterial pressure at mid trimester was not signicant. There was an increasing trend of mean arterial pressure as duration of pregnancy advances. PIH is multifactorial. Failure Conclusion: of fall in mean arterial pressure in mid trimester alone cannot be used as a predictor of PIH.

scholarly journals Brain Testosterone-CYP1B1 (Cytochrome P450 1B1) Generated Metabolite 6β-Hydroxytestosterone Promotes Neurogenic Hypertension and Inflammation

Hypertension ◽  
2020 ◽  
Vol 76 (3) ◽  
pp. 1006-1018
Author(s):  
Purnima Singh ◽  
Shubha Ranjan Dutta ◽  
Chi Young Song ◽  
SaeRam Oh ◽  
Frank J. Gonzalez ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Cytochrome P450 ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Paraventricular Nucleus ◽  
Male Mice ◽  
Cytochrome P450 1B1 ◽  
Induced Hypertension ◽  
The Brain

Previously, we showed that peripheral administration of 6β-hydroxytestosterone, a CYP1B1 (cytochrome P450 1B1)-generated metabolite of testosterone, promotes angiotensin II-induced hypertension in male mice. However, the site of action and the underlying mechanism by which 6β-hydroxytestosterone contributes to angiotensin II-induced hypertension is not known. Angiotensin II increases blood pressure by its central action, and CYP1B1 is expressed in the brain. This study was conducted to determine whether testosterone-CYP1B1 generated metabolite 6β-hydroxytestosterone locally in the brain promotes the effect of systemic angiotensin II to produce hypertension in male mice. Central CYP1B1 knockdown in wild-type ( Cyp1b1 +/+ ) mice by intracerebroventricular-adenovirus-GFP (green fluorescence protein)-CYP1B1-short hairpin (sh)RNA attenuated, whereas reconstitution of CYP1B1 by adenovirus-GFP-CYP1B1-DNA in the paraventricular nucleus but not in subfornical organ in Cyp1b1 −/− mice restored angiotensin II-induced increase in systolic blood pressure measured by tail-cuff. Intracerebroventricular-testosterone in orchidectomized (Orchi)- Cyp1b1 +/+ but not in Orchi- Cyp1b1 −/− , and intracerebroventricular-6β-hydroxytestosterone in the Orchi- Cyp1b1 −/− mice restored the angiotensin II-induced: (1) increase in mean arterial pressure measured by radiotelemetry, and autonomic imbalance; (2) reactive oxygen species production in the subfornical organ and paraventricular nucleus; (3) activation of microglia and astrocyte, and neuroinflammation in the paraventricular nucleus. The effect of intracerebroventricular-6β-hydroxytestosterone to restore the angiotensin II-induced increase in mean arterial pressure and autonomic imbalance in Orchi- Cyp1b1 −/− mice was inhibited by intracerebroventricular-small interfering (si)RNA-androgen receptor (AR) and GPRC6A (G protein-coupled receptor C6A). These data suggest that testosterone-CYP1B1-generated metabolite 6β-hydroxytestosterone, most likely in the paraventricular nucleus via AR and GPRC6A, contributes to angiotensin II-induced hypertension and neuroinflammation in male mice.

scholarly journals Measurement of mean arterial pressure: comparison of the Vasotrac monitor with the finger differential oscillometric device

2010 ◽  
pp. 691-696 ◽  
Author(s):  
K Jagomägi ◽  
R Raamat ◽  
J Talts ◽  
U Ragun ◽  
P Tähepõld
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Radial Artery ◽  
Blood Pressure Monitoring ◽  
Signal Conditioning ◽  
Non Invasive ◽  
Arterial Blood ◽  
Oscillometric Device ◽  
Good Agreement

The Vasotrac monitor provides non-invasive near-continuous blood pressure monitoring and is designed to be an alternative to direct intra-arterial blood pressure (BP) measurement. As compared to radial artery invasive BP and upper arm noninvasive BP, Vasotrac readings have been found to have a good agreement with them. However, discrepancies have been reported when rapid changes in BP exist. In the present study we compared BP measured by the Vasotrac monitor on the radial artery with that recorded on the finger arteries by the differential oscillometric device allowing measurement on the beat-to-beat basis. Comparisons were performed on the mean arterial pressure (MAP) level. Special attention was paid to the signal conditioning before comparison of pressures of different temporal resolution. Altogether 383 paired MAP measurements were made in 14 healthy subjects. Based on all 383 paired measurements, the MAP values measured at the radial artery at rest were 4.8±6.0 mm Hg higher than those measured on fingers. The observed difference between the Vasotrac and differential oscillometric device can be explained by different measurement sites. This result is consistent with previous investigations, and the Vasotrac monitor can be considered to adequately track relatively rapid MAP changes on the radial artery. Attention should be paid to a proper signal conditioning before comparison of results obtained by different devices.

CHARACTERISTICS OF 24-HOUR BLOOD PRESSURE INDICATORS IN PATIENTS WITH HYPERTENSION AND CHRONIC OBSTRUCTIVE PULMONARY DISEASE

2020 ◽  
pp. 31-41
Author(s):  
M.A. Bubnova ◽  
O.N. Kryuchkova
Keyword(s):  
Blood Pressure ◽  
Chronic Obstructive Pulmonary Disease ◽  
Mean Arterial Pressure ◽  
High Risk ◽  
Arterial Pressure ◽  
Pulmonary Disease ◽  
Comparison Group ◽  
Cardiovascular Complications ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease

Patients with hypertension (HT) and chronic obstructive pulmonary disease (COPD) have a high risk of cardiovascular complications. Up to now, there is no optimal strategy for combined antihypertensive therapy. Still, the data of 24-hour blood pressure monitoring (BPM) are important while choosing treatment tactics. The aim of the paper is to study the features of indicators in patients with arterial hypertension (AH) and COPD. Materials and methods. 130 patients with HT were included in the study. The main group (n=90) included comorbid patients with HT and COPD, their average age was 61.30±1.01; the comparison group (n=40) consisted of patients with HT, their average age was 59.10±1.53. All patients underwent 24-hour BPM. Results. Comorbid patients revealed an increase in the mean 24-hour and night systolic and mean arterial pressure values as well as a significant increase in the load index of systolic, diastolic and mean arterial pressure. Also, comorbid patients demonstrated higher blood pressure in contrast to the patients of the comparison group. They had increased systolic, diastolic and mean blood pressure variability and a quicker rate of morning blood pressure rise. According to 24-hour blood pressure dynamics, pathological types of the 24-hour blood pressure curve, a higher frequency of the night-peaker profile dominated in patients with COPD if compared to patients with HT. Conclusion. The obtained data indicated a high risk of cardiovascular complications in comorbid patients, early target organ damage and an unfavorable disease prognosis. It means that both further study of hypertension clinical course in such patients and personalization of antihypertensive therapy are relevant. Keywords: hypertension, chronic obstructive pulmonary disease, 24-hour monitoring, blood pressure. Пациенты с артериальной гипертензией (АГ) и хронической обструктивной болезнью легких (ХОБЛ) имеют высокий риск возникновения кардиоваскулярных осложнений. В настоящее время в лечении не определена наиболее оптимальная стратегия комбинированной антигипертензивной терапии. Для выбора тактики терапии важную роль играют показатели суточного мониторирования артериального давления (СМАД). Цель. Изучить особенности показателей СМАД у пациентов с АГ на фоне ХОБЛ. Материалы и методы. В исследование включено 130 пациентов с АГ. В основную группу (n=90) вошли пациенты с АГ и ХОБЛ (средний возраст – 61,30±1,01 года), в группу сравнения (n=40) – больные только АГ (средний возраст – 59,10±1,53 года). Всем пациентам проведено СМАД. Результаты. У пациентов с коморбидностью выявлены следующие особенности суточных показателей артериального давления: увеличение значений среднесуточных и средненочных показателей систолического и среднего артериального давления; существенное повышение индекса нагрузки систолическим, диастолическим и средним артериальным давлением. Также эти больные отличались от пациентов группы сравнения более высокими значениями пульсового давления, имели повышенную вариабельность систолического, диастолического и среднего артериального давления, у них наблюдалось увеличение скорости утреннего подъема артериального давления. Суточная динамика артериального давления у пациентов с ХОБЛ характеризовалась преобладанием патологических типов суточной кривой АД, более высокой частотой профиля night-peaker по сравнению с больными только АГ. Выводы. Выявленные особенности свидетельствуют о высоком риске сердечно-сосудистых осложнений у пациентов с коморбидностью, раннем поражении органов-мишеней и неблагоприятном прогнозе заболевания, что требует дальнейшего изучения особенностей клинического течения АГ у таких больных и индивидуализации антигипертензивной терапии. Ключевые слова: артериальная гипертензия, хроническая обструктивная болезнь легких, суточное мониторирование, артериальное давление.

scholarly journals Plasticity in breathing and arterial blood pressure following acute intermittent hypercapnic hypoxia in infant rat pups with a partial loss of 5-HT neurons

2015 ◽  
Vol 309 (10) ◽  
pp. R1273-R1284 ◽  
Author(s):  
Jennifer Magnusson ◽  
Kevin J. Cummings
Keyword(s):  
Blood Pressure ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Arterial Blood Pressure ◽  
Cardiovascular Responses ◽  
Partial Loss ◽  
Rat Pups ◽  
Arterial Blood ◽  
Hypercapnic Hypoxia ◽  
Long Term Facilitation

The role of serotonin (5-HT) neurons in cardiovascular responses to acute intermittent hypoxia (AIH) has not been studied in the neonatal period. We hypothesized that a partial loss of 5-HT neurons would reduce arterial blood pressure (BP) at rest, increase the fall in BP during hypoxia, and reduce the long-term facilitation of breathing (vLTF) and BP following AIH. We exposed 2-wk-old, 5,7-dihydroxytryptamine-treated and controls to AIH (10% O2; n = 13 control, 14 treated), acute intermittent hypercapnia (5% CO2; n = 12 and 11), or acute intermittent hypercapnic hypoxia (AIHH; 10% O2, 5% CO2; n = 15 and 17). We gave five 5-min challenges of AIH and acute intermittent hypercapnia, and twenty ∼20-s challenges of AIHH to mimic sleep apnea. Systolic BP (sBP), diastolic BP, mean arterial pressure, heart rate (HR), ventilation (V̇e), and metabolic rate (V̇o2) were continuously monitored. 5,7-Dihydroxytryptamine induced an ∼35% loss of 5-HT neurons from the medullary raphe. Compared with controls, pups deficient in 5-HT neurons had reduced resting sBP (∼6 mmHg), mean arterial pressure (∼5 mmHg), and HR (56 beats/min), and experienced a reduced drop in BP during hypoxia. AIHH induced vLTF in both groups, reflected in increased V̇e and V̇e/V̇o2, and decreased arterial Pco2. The sBP of pups deficient in 5-HT neurons, but not controls, was increased 1 h following AIHH. Our data suggest that a relatively small loss of 5-HT neurons compromises resting BP and HR, but has no influence on ventilatory plasticity induced by AIHH. AIHH may be useful for reversing cardiorespiratory defects related to partial 5-HT system dysfunction.

Hypotensive and Regional Haemodynamic Effects of Exercise, Fasted and after Food, in Human Sympathetic Denervation

1998 ◽  
Vol 94 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Sharmini Puvi-Rajasingham ◽  
Gareth D. P. Smith ◽  
Adeola Akinola ◽  
Christopher J. Mathias
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Superior Mesenteric Artery ◽  
Vascular Resistance ◽  
Mesenteric Artery ◽  
Autonomic Failure ◽  
Sympathetic Denervation ◽  
Stroke Distance

1. In human sympathetic denervation due to primary autonomic failure, food and exercise in combination may produce a cumulative blood pressure lowering effect due to simultaneous splanchnic and skeletal muscle dilatation unopposed by corrective cardiovascular reflexes. We studied 12 patients with autonomic failure during and after 9 min of supine exercise, when fasted and after a liquid meal. Standing blood pressure was also measured before and after exercise. 2. When fasted, blood pressure fell during exercise from 162 ± 7/92 ± 4 to 129 ± 9/70 ± 5 mmHg (mean arterial pressure by 22 ± 5%), P < 0.0005. After the meal, blood pressure fell from 159 ± 8/88 ± 6 to 129 ± 6/70 ± 4 mmHg (mean arterial pressure by 22 ± 3%), P < 0.0001, and further during exercise to 123 ± 6/61 ± 3 mmHg (mean arterial pressure by 9 ± 3%), P < 0.01. The stroke distance—heart rate product, an index of cardiac output, did not change after the meal. During exercise, changes in the stroke distance—heart rate product were greater when fasted. 3. Resting forearm and calf vascular resistance were higher when fasted. Calf vascular resistance fell further after exercise when fasted. Resting superior mesenteric artery vascular resistance was lower when fed; 0.19 ± 0.02 compared with 032 ± 0.06, P < 0.05. After exercise, superior mesenteric artery vascular resistance had risen by 82%, to 0.53 ± 0.12, P < 0.05 (fasted) and by 47%, to 0.29 ± 0.05, P < 0.05 (fed). 4. On standing, absolute levels of blood pressure were higher when fasted [83 ± 7/52 ± 7 compared with 71 ± 2/41 ± 3 (fed), each P < 0.05]. Subjects were more symptomatic on standing post-exercise when fed. 5. In human sympathetic denervation, exercise in the fed state lowered blood pressure further than when fasted and worsened symptoms of postural hypotension.

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