Mechanisms in the pressor effects of hepatic portal venous fatty acid infusion

1997 ◽  
Vol 273 (1) ◽  
pp. R324-R330 ◽  
Author(s):  
R. J. Grekin ◽  
C. J. Dumont ◽  
A. P. Vollmer ◽  
S. W. Watts ◽  
R. C. Webb

Portal venous infusion of oleate solution has pressor effects. We have examined efferent mechanisms, measured the response to sustained infusion, and determined the effect of linoleate. Eight conscious animals received concurrent infusions of prazosin or vehicle with portal venous infusion of oleate. Oleate alone increased mean arterial pressure from 109.0 +/- 4.1 to 123.0 +/- 5.8 mmHg (P = 0.02), whereas no increase in blood pressure occurred when oleate was infused with prazosin. In 10 rats, concurrent infusion of losartan had no effect on the pressor activity of portal oleate infusion. Twenty-two animals received portal oleate or vehicle as a continuous infusion for 7 days. Mean arterial pressure (126.1 +/- 2.0 vs. 107.8 +/- 2.6 mmHg, P < 0.001) and heart rate (383 +/- 5 vs. 366 +/- 5, P = 0.0257) were increased in oleate-infused animals. No differences in plasma fatty acids, glucose, insulin, pressor hormones, liver enzymes, or in vitro arterial pressor responsiveness were observed. Portal venous infusion of linoleate increased arterial pressure by 12.2 +/- 3.2 mmHg (P = 0.033). These results indicate that alpha-adrenergic activity is necessary for the acute pressor effects of portal oleate, that sustained portal oleate infusion results in persistent blood pressure elevation, and that other long-chain fatty acids besides oleate have pressor effects.

1996 ◽  
Vol 271 (6) ◽  
pp. R1759-R1769 ◽  
Author(s):  
B. N. Van Vliet ◽  
L. Hu ◽  
T. Scott ◽  
L. Chafe ◽  
J. P. Montani

We investigated cardiac morphometry 6 wk after sinoaortic baroreceptor denervation (SAD) in Long-Evans rats. SAD (n = 19) was associated with an 11% increase in the weight of the left ventricle (LV) plus septum (P < 0.001) and a 39% increase in that of the right ventricular (RV) free wall (P < 0.001), relative to sham-operated rats (n = 18). RV wall thickness was significantly increased in SAD animals, but there was no difference in the LV wall thickness and volumes of the RV and LV between groups. Constrictor responses to methoxamine and dilation responses to acetylcholine were assessed in an in vitro perfused mesenteric circulation preparation, but neither response was affected by SAD. Baroreceptor denervation was associated with marked and significant increases in the variability (2.8-fold) and daily peak (39 mmHg) levels of telemetered mean arterial pressure (MAP) and small (5%) but significant increases in the daily mean MAP level. Our results are consistent with an effect of increased MAP variability on ventricular weight but cannot rule out possible contributions from other mechanisms.


Author(s):  
Ninitha Asirvatham-Jeyaraj ◽  
Madeline M. Gauthier ◽  
Christopher T. Banek ◽  
Abhismitha Ramesh ◽  
Hannah Garver ◽  
...  

Renal denervation (RDNX) lowers mean arterial pressure (MAP) in patients with resistant hypertension. Less well studied is the effect of celiac ganglionectomy (CGX), a procedure which involves the removal of the nerves innervating the splanchnic vascular bed. We hypothesized that RDNX and CGX would both lower MAP in genetically hypertensive Schlager (BPH/2J) mice through a reduction in sympathetic tone. Telemeters were implanted into the femoral artery in mice to monitor MAP before and after RDNX (n=5), CGX (n=6), or SHAM (n=6). MAP, systolic blood pressure, diastolic blood pressure, and heart rate were recorded for 14 days postoperatively. The MAP response to hexamethonium (10 mg/kg, IP) was measured on control day 3 and postoperative day 10 as a measure of global neurogenic pressor activity. The efficacy of denervation was assessed by measurement of tissue norepinephrine. Control MAP was similar among the 3 groups before surgical treatments (≈130 mm Hg). On postoperative day 14, MAP was significantly lower in RDNX (−11±2 mm Hg) and CGX (−11±1 mm Hg) groups compared with their predenervation values. This was not the case in SHAM mice (−5±3 mm Hg). The depressor response to hexamethonium in the RDNX group was significantly smaller on postoperative day 10 (−10±5 mm Hg) compared with baseline control (−25±10 mm Hg). This was not the case in mice in the SHAM (day 10; −28±5 mm Hg) or CGX (day 10; −34±7 mm Hg) group. In conclusion, both renal and splanchnic nerves contribute to hypertension in BPH/2J mice, but likely through different mechanisms.


Author(s):  
Noah Manring ◽  
Mouayed Al-Toki

Abstract Aortic compliance has been well established as an independent predictor of cardiovascular morbidity and mortality. The current "gold standard" for assessing aortic compliance is to use the carotid-femoral pulse-wave velocity (PWV) as a surrogate; however, PWV alone has been discussed in the literature as being inadequate for assessing compliance, especially for elderly patients and others who have a stiff aorta. In this paper an equation for the aortic compliance is developed using two approaches: 1) lumped-parameter modeling based on blood-pressure data and 2) distributed modeling based on the PWV. In-vitro experiments are conducted using a silicone-rubber tube which simulates the aorta, and an actual aorta harvested from a 1-year old, Holstein heifer. For both the rubber aorta and the Holstein aorta, a comparison is made between the blood-pressure model and the PWV model. In conclusion it is shown that good agreement exists between the two models, suggesting that either model may be used depending upon the available data. Furthermore, due to differences in material properties, it is shown that the compliance of the rubber aorta increases with mean arterial-pressure, while the compliance of the Holstein aorta decreases with mean arterial-pressure. Clinical implications of this research are also discussed.


Author(s):  
M.A. Bubnova ◽  
O.N. Kryuchkova

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.


2015 ◽  
Vol 309 (10) ◽  
pp. R1273-R1284 ◽  
Author(s):  
Jennifer Magnusson ◽  
Kevin J. Cummings

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.


1998 ◽  
Vol 94 (1) ◽  
pp. 49-55 ◽  
Author(s):  
Sharmini Puvi-Rajasingham ◽  
Gareth D. P. Smith ◽  
Adeola Akinola ◽  
Christopher J. Mathias

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.


2002 ◽  
Vol 93 (6) ◽  
pp. 1966-1972 ◽  
Author(s):  
Maria T. E. Hopman ◽  
Jan T. Groothuis ◽  
Marcel Flendrie ◽  
Karin H. L. Gerrits ◽  
Sibrand Houtman

The purpose of the present study was to determine the effect of a spinal cord injury (SCI) on resting vascular resistance in paralyzed legs in humans. To accomplish this goal, we measured blood pressure and resting flow above and below the lesion (by using venous occlusion plethysmography) in 11 patients with SCI and in 10 healthy controls (C). Relative vascular resistance was calculated as mean arterial pressure in millimeters of mercury divided by the arterial blood flow in milliliters per minute per 100 milliliters of tissue. Arterial blood flow in the sympathetically deprived and paralyzed legs of SCI was significantly lower than leg blood flow in C. Because mean arterial pressure showed no differences between both groups, leg vascular resistance in SCI was significantly higher than in C. Within the SCI group, arterial blood flow was significantly higher and vascular resistance significantly lower in the arms than in the legs. To distinguish between the effect of loss of central neural control vs. deconditioning, a group of nine SCI patients was trained for 6 wk and showed a 30% increase in leg blood flow with unchanged blood pressure levels, indicating a marked reduction in vascular resistance. In conclusion, vascular resistance is increased in the paralyzed legs of individuals with SCI and is reversible by training.


2016 ◽  
Vol 125 (4) ◽  
pp. 732-743 ◽  
Author(s):  
Hiroshi Sunaga ◽  
John J. Savarese ◽  
Jeff D. McGilvra ◽  
Paul M. Heerdt ◽  
Matthew R. Belmont ◽  
...  

Abstract Background CW002, a novel nondepolarizing neuromuscular blocking agent of intermediate duration, is degraded in vitro by l-cysteine; CW002-induced neuromuscular blockade (NMB) is antagonized in vivo by exogenous l-cysteine.1 Further, Institutional Animal Care and Use Committee–approved studies of safety and efficacy in eight anesthetized monkeys and six cats are described. Methods Mean arterial pressure, heart rate, twitch, and train-of-four were recorded; estimated dose producing 95% twitch inhibition (ED95) for NMB and twitch recovery intervals from 5 to 95% of baseline were derived. Antagonism of 99 to 100% block in monkeys by l-cysteine (50 mg/kg) was tested after bolus doses of approximately 3.75 to 20 × ED95 and after infusions. Vagal and sympathetic autonomic responses were recorded in cats. Dose ratios for [circulatory (ED20) or autonomic (ED50) changes/ED95 (NMB)] were calculated. Results ED95s of CW002 in monkeys and cats were 0.040 and 0.035 mg/kg; l-cysteine readily antagonized block in monkeys: 5 to 95% twitch recovery intervals were shortened to 1.8 to 3.6 min after 3.75 to 10 × ED95 or infusions versus 11.5 to 13.5 min during spontaneous recovery. ED for 20% decrease of mean arterial pressure (n = 27) was 1.06 mg/kg in monkeys; ED for 20% increase of HR (n = 27) was 2.16 mg/kg. ED50s for vagal and sympathetic inhibition in cats were 0.59 and &gt;&gt;0.80 mg/kg (n = 14 and 15). Dose ratios for [circulatory or autonomic changes/ED95 (NMB)] were all more than 15 × ED95. Conclusions The data further verify the neuromuscular blocking properties of CW002, including rapid reversal by l-cysteine of 100% NMB under several circumstances. A notable lack of autonomic or circulatory effects provided added proof of safety and efficacy.


Author(s):  
Sidharth Sraban Routray ◽  
Ramakanta Mohanty

ABSTRACTObjective: During laparoscopic surgeries, pneumoperitoneum can lead to various pathophysiologic changes in the cardiovascular system resulting inhypertension and tachycardia. Search for ideal drug to prevent this hemodynamic response goes on. The aim of our study was to evaluate the effect oforally administered moxonidine in attenuating the hemodynamic responses that occur during the laparoscopic surgeries.Methods: A total of 50 adult acetylsalicylic acid I and II patients scheduled for elective laparoscopic surgeries were selected for this prospectiverandomized double-blinded study. They were randomly allocated into two groups: moxonidine group (M) and placebo group (P). M group receivedoral moxonidine 0.3 mg at 8 pm on the day before surgery and at 8 am on the day of surgery. P group received a placebo at the same timing as that ofthe M group.Results: Following pneumoperitoneum rise in systolic blood pressure (SBP), diastolic BP (DBP), mean arterial pressure (MAP), and heart rate (HR)was higher in P group in comparison to M group which was statistically significant.Conclusion: Significant rise in HR, SBP, DBP, and mean BP was noted in the P group in comparison to moxonidine group. Moxonidine provided betterperioperative hemodynamic stability in patients undergoing laparoscopic surgeries.Keywords: Moxonidine, Stress response, Laparoscopic.


1999 ◽  
Vol 91 (3) ◽  
pp. 677-677 ◽  
Author(s):  
Basil F. Matta ◽  
Karen J. Heath ◽  
Kate Tipping ◽  
Andrew C. Summors

Background The effect of volatile anesthetics on cerebral blood flow depends on the balance between the indirect vasoconstrictive action secondary to flow-metabolism coupling and the agent's intrinsic vasodilatory action. This study compared the direct cerebral vasodilatory actions of 0.5 and 1.5 minimum alveolar concentration (MAC) sevoflurane and isoflurane during an propofol-induced isoelectric electroencephalogram. Methods Twenty patients aged 20-62 yr with American Society of Anesthesiologists physical status I or II requiring general anesthesia for routine spinal surgery were recruited. In addition to routine monitoring, a transcranial Doppler ultrasound was used to measure blood flow velocity in the middle cerebral artery, and an electroencephalograph to measure brain electrical activity. Anesthesia was induced with propofol 2.5 mg/kg, fentanyl 2 micro/g/kg, and atracurium 0.5 mg/kg, and a propofol infusion was used to achieve electroencephalographic isoelectricity. End-tidal carbon dioxide, blood pressure, and temperature were maintained constant throughout the study period. Cerebral blood flow velocity, mean blood pressure, and heart rate were recorded after 20 min of isoelectric encephalogram. Patients were then assigned to receive either age-adjusted 0.5 MAC (0.8-1%) or 1.5 MAC (2.4-3%) end-tidal sevoflurane; or age-adjusted 0.5 MAC (0.5-0.7%) or 1.5 MAC (1.5-2%) end-tidal isoflurane. After 15 min of unchanged end-tidal concentration, the variables were measured again. The concentration of the inhalational agent was increased or decreased as appropriate, and all measurements were repeated again. All measurements were performed before the start of surgery. An infusion of 0.01% phenylephrine was used as necessary to maintain mean arterial pressure at baseline levels. Results Although both agents increased blood flow velocity in the middle cerebral artery at 0.5 and 1.5 MAC, this increase was significantly less during sevoflurane anesthesia (4+/-3 and 17+/-3% at 0.5 and 1.5 MAC sevoflurane; 19+/-3 and 72+/-9% at 0.5 and 1.5 MAC isoflurane [mean +/- SD]; P&lt;0.05). All patients required phenylephrine (100-300 microg) to maintain mean arterial pressure within 20% of baseline during 1.5 MAC anesthesia. Conclusions In common with other volatile anesthetic agents, sevoflurane has an intrinsic dose-dependent cerebral vasodilatory effect. However, this effect is less than that of isoflurane.


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