Femoral Pressure Research Articles

Atrial natriuretic peptide decreases aorta stiffness in cholesterol-fed anesthetized rabbits

Aortas from Watanabe heritable hyperlipidemic rabbits show in vitro impaired vasodilatory response to atrial natriuretic peptide (ANP) during atherosclerosis progression. To test a similar reaction in vivo, the effect of ANP administration on pulse wave velocity (PWV, index of aorta stiffness) was investigated in 10 normal and 10 cholesterol-fed (2% cholesterol-loaded feeding for 4 weeks) anesthetized male New Zealand White (NZW) rabbits. Invasively taken carotid and femoral blood pressures (BP) were recorded, simultaneously with ECG, and blood samples for ANP measurement (by RIA) were taken at 0 min and 20, 40, 60 min following an intravenous 20-min administration of either 0.2 μg kg −1 min −1 hANP in 5 ml normal saline or only 5 ml saline. Mild to moderate atherosclerosis was found in ascending aorta. BP decreased by ANP only at 20 min in both groups, whereas only in cholesterol-fed rabbits the borderline ( p = 0.09) increased at 0 min PWV was lowered ( p = 0.008) in all recording times. With any degree of increase of systolic BP (SBP) PWV increased less in ANP receivers. Atherosclerosis and SBP were the most important determinants of PWV and the effect of ANP was independent of confounding factors. It is concluded that short-term ANP administration in doses to achieve levels approximately threefold the pretreatment ones in normal and mildly to moderately atherosclerotic anesthetized NZW rabbits, causes an improvement of aorta stiffness only in atherosclerotic rabbits.

Heterogeneity in age related central arterial stiffening: ascending aortic stiffness is a better predictor of carotid to femoral pulse wave velocity and brachial peripheral blood pressure than carotid stiffness

Heterogeneity in age related central arterial stiffening: ascending aortic stiffness is a better predictor of carotid to femoral pulse wave velocity and brachial peripheral blood pressure than carotid stiffness

Hemodynamic and Biochemical Changes during Total Hepatic Vascular Exclusion in Dogs

Twelve healthy Beagles were divided into 3 groups of 4 dogs each. To compare 2 methods of total hepatic vascular exclusion (THVE), we investigated the hemodynamic changes during THVE and assessed the influences on hepatic, renal and pancreatic biochemistry and the complications after THVE. In Group A, the thoracic aorta, hepatic pedicle and prehepatic and posthepatic caudal vena cava were occluded for 20 min, while in Group B, the celiac and cranial mesenteric arteries, hepatic pedicle and prehepatic and posthepatic caudal vena cava were occluded for 20 min. In Group C, a sham operation was performed. The arterial, venous and portal venous pressures and serum biochemistry parameters were measured before and during THVE and for 30 min after reperfusion. The carotid arterial pressure did not change in Group A during THVE, but decreased in Group B. The femoral and portal venous pressures in Group B increased significantly during THVE compared with those in Group C. With the exception of alanine aminotransferase, the serum biochemical profiles remained unchanged after the operation. For 7 days after the operation, no complications were observed in any of the dogs. In conclusion, occlusion of thoracic aorta, hepatic pedicle and prehepatic and posthepatic caudal vena cava is a feasible and safe method of hepatic vascular occlusion. This technique appears to be effective for canine hepatic surgery, such as removal of a large right-divisional hepatic tumor and attenuation of intrahepatic portosystemic shunt.

Hypertensive extracorporeal limb perfusion (HELP): A new technique for managing critical lower limb ischemia

The concept of repeatedly connecting an extracorporeal blood pump to produce pancycle suprasystolic inflow pressures to ischemic limbs is introduced. Balloon catheters allow for limb isolation from the systemic circulation. In the acute phase, it is assumed that pressure is proportion to flow (Poiseuille's Law) and in the chronic phase that collateral growth is related to endothelial shear stress and wall tension. The primary objective was to establish that increased flow could be achieved through collateral circulation in animals and in man with extracorporeal limb hyperperfusion. The second objective was to develop and test an arterial access system capable of intermittent regional hyperperfusion similar in concept to intermittent hemodialysis. Finally, to demonstrate the translocation of these concepts into humans facing major limb amputation where all standard treatment options had been exhausted. Twelve sheep (6 hyperperfusion and 6 controls) were attached to a cardiac vortex pump and perfused at 200 mm Hg pancycle with the superficial femoral artery doubly ligated and isolated from the systemic circulation with a balloon catheter. Pressure transducers measured carotid and distal femoral pressures and the carotid-femoral index was calculated. To allow hyperperfusion to be repeated transcutaneously, a peripheral access system (PAS [Allvascular, St Leonards, New South Wales, Australia]) was constructed. This device was implanted in the common carotid artery in 8 sheep and opened approximately 3 days a week for continuous arterial access up to 37 days for 67 openings. To demonstrate these principles in humans, 3 patients with critically ischemic limbs were hyperperfused intermittently. Digital thermography compared the other limb as controls and provided objective evidence of the vascular changes. The mean carotid-femoral index was 0.6 +/- 0.01 for controls compared with 1.1 +/- 0.28 for the hyperperfusion group (P < .001). The collateral flow was superior to normal flow (ie, with the superficial femoral not occluded). Continuous access to the carotid arterial tree via the access device was 25.3 +/- 8.8 days with 5 of 8 devices open for the entire observational period (maximum 37 days). The human ischemic limbs were hyperperfused at 2-4 times the mean arterial pressure producing 3-6 times an increase in pump flow measurements intermittently for 53 +/- 16 hours. The clinical findings of rest pain, paresthesia, capillary return, and movement showed dramatic improvement as did thermographic emissions. Major amputation was avoided in the cases presented. Blood flow through collaterals can be very significantly augmented by connection to an extracorporeal pump with isolation from the systemic circulation. The pancycle hyperperfusion can be safely repeated by implantation of an arterial access device. In the longer term, there is evidence of collateral development. When amputation is the only alternative, hypertensive extracorporeal limb perfusion should be considered.

Toward a noninvasive subject-specific estimation of abdominal aortic pressure

A method for estimation of central arterial pressure based on linear one-dimensional wave propagation theory is presented in this paper. The equations are applied to a distributed model of the arterial tree, truncated by three-element windkessels. To reflect individual differences in the properties of the arterial trees, we pose a minimization problem from which individual parameters are identified. The idea is to take a measured waveform in a peripheral artery and use it as input to the model. The model subsequently predicts the corresponding waveform in another peripheral artery in which a measurement has also been made, and the arterial tree model is then calibrated in such a way that the computed waveform matches its measured counterpart. For the purpose of validation, invasively recorded abdominal aortic, brachial, and femoral pressures in nine healthy subjects are used. The results show that the proposed method estimates the abdominal aortic pressure wave with good accuracy. The root mean square error (RMSE) of the estimated waveforms was 1.61 +/- 0.73 mmHg, whereas the errors in systolic and pulse pressure were 2.32 +/- 1.74 and 3.73 +/- 2.04 mmHg, respectively. These results are compared with another recently proposed method based on a signal processing technique, and it is shown that our method yields a significantly (P < 0.01) lower RMSE. With more extensive validation, the method may eventually be used in clinical practice to provide detailed, almost individual, specific information as a valuable basis for decision making.

Optimisation of the posterior stabilised tibial post for greater femoral rollback after total knee arthroplasty—a finite element analysis

Femoral rollback after total knee arthroplasty (TKA) is necessary for flexion beyond 90-100 degrees. Femoral rollback in posterior cruciate substituting TKA occurs as a result of the interaction between the femoral cam and tibial post. The geometric design of the cam post mechanism determines the kinematics of rollback. The purpose of this study is to optimise the design of the femoral cam-tibial post articulation through finite element analysis and suggest various design parameters that would optimise femoral rollback. Modifications to the tibial post geometry without changing the relative post position or slope are made. Results are characterised in terms femoral rollback and pressure distribution at the tibial post. Small design modifications to the tibial post are seen to produce large changes in femoral rollback with relatively small accompanying increases in contact pressures at the tibial post.

Comparative study of methodologies for pulse wave velocity estimation

Arterial stiffness, estimated by pulse wave velocity (PWV), is an independent predictor of cardiovascular mortality and morbidity. However, the clinical applicability of these measurements and the elaboration of reference PWV values are difficult due to differences between the various devices used. In a population of 50 subjects aged 20-84 years, we compared PWV measurements with three frequently used devices: the Complior and the PulsePen, both of which determine aortic PWV as the delay between carotid and femoral pressure wave and the PulseTrace, which estimates the Stiffness Index (SI) by analyzing photoplethysmographic waves acquired on the fingertip. PWV was measured twice by each device. Coefficient of variation of PWV was 12.3, 12.4 and 14.5% for PulsePen, Complior and PulseTrace, respectively. These measurements were compared with the reference method, that is, a simultaneous acquisition of pressure waves using two tonometers. High correlation coefficients with the reference method were observed for PulsePen (r = 0.99) and Complior (r = 0.83), whereas for PulseTrace correlation with the reference method was much lower (r = 0.55). Upon Bland-Altman analysis, mean differences of values +/- 2s.d. versus the reference method were -0.15 +/- 0.62 m/s, 2.09 +/- 2.68 m/s and -1.12 +/- 4.92 m/s, for PulsePen, Complior and Pulse-Trace, respectively. This study confirms the reliability of Complior and PulsePen devices in estimating PWV, while the SI determined by the PulseTrace device was found to be inappropriate as a surrogate of PWV. The present results indicate the urgent need for evaluation and comparison of the different devices to standardize PWV measurements and establish reference values.

The Reamer/Irrigator/Aspirator Reduces Femoral Canal Pressure in Simulated TKA

Inserting the femoral intramedullary alignment rod during total knee arthroplasty (TKA) can generate high intramedullary pressure, which increases the risk of intraoperative complications caused by fat embolism. Despite modifications to the surgical procedure, the best method to prevent this increase in pressure remains unknown. The reamer/irrigator/aspirator is a surgical instrument designed for use during femoral canal entry to increase the canal size and remove intramedullary fat and may prevent this pressure increase. We posed two hypotheses: (1) using the reamer/irrigator/aspirator system will result in lower maximum femoral intramedullary pressure than using only conventional instrumentation during the initial steps of a TKA; and (2) using the reamer/irrigator/aspirator system in the initial steps of TKA will result in a mean maximum intramedullary pressure less than 200 mm Hg. We simulated a TKA on 14 cadaveric femurs to compare the femoral intramedullary pressure using both methods. Considerable decreases in femoral intramedullary pressure of 86% proximally and 87% distally were obtained by using the reamer/irrigator/aspirator system. The mean maximum pressure using the reamer/irrigator/aspirator system was less than 200 mm Hg. Additional clinical studies are needed to confirm any reduction in complications using the reamer/irrigator/aspirator system.

Thoracic endovascular aortic repair of adult patent ductus arteriosus with pulmonary hypertension

of the fear of more distal embolization. The patient was taken to the operating room soon after the diagnosis was made. An interesting situation arose when the device could not be found in the ascending aorta, where it was initially reported to be present. We think that initiation of femoral bypass resulted in the device being pushed back into the proximal aorta. With subsequent aortic crossclamping and antegrade cold blood cardioplegia, it slipped through the aortic valve into the left ventricle and got entangled in the submitral apparatus. The decision to start the patient on deep hypothermia with plans of circulatory arrest was made for fear of distal embolization during aortic manipulation. It seems that the femoral artery bypass pressure helped by pushing the device back near the aortic valve and, with subsequent antegrade cardioplegia, pushed the device through the aortic valve into the left ventricle and then toward the left atrium, and this saved the patient from an aortic intervention. This phenomenon has not been described in the literature to the best of our knowledge. We propose that when an ASO has embolized to the aorta, femoral cannulation and cardiopulmonary bypass, along with transesophageal echocardiography and fluoroscopy to localize the device accurately, should be used.

Retrograde aortic perfusion dislodges a dislodged Amplatzer device

Retrograde aortic perfusion dislodges a dislodged Amplatzer device

Neuropeptide Y and age‐related development of hypertension in the rat

Essential hypertension is associated with increased sympathetic nerve activity in both animals and humans. We tested the hypothesis that neuropeptide Y (NPY) Y1 receptor activation was involved in the development of hypertension. In vivo infusions of NPY (15μg/kg) and Phenylephrine (PE, 10nmol/kg) to the intact hindlimb of spontaneously hypertensive rats (SHR) and their genetic control Wistar‐Kyoto (WKY) rats were performed in animals of 3, 5 and 7 weeks of age (n = 2–3 animals per strain per age). Femoral blood flow, blood pressure and heart rate were measured, while hindlimb vascular conductance (CHL), were calculated as an indicator of vascular responsiveness. Following phenylephrine (PE) infusions, CHL in the 7 week old SHR and WKY animals fell by 58.5% and 49.2% respectively (p&lt;0.05). The response remained depressed in both strains for at least 100s (p&lt;0.05). Compared with baseline, NPY infusion produced a 69% fall in CHL in the SHR that remained depressed for 100s (p&lt;0.05). No effect of NPY was observed in the 7 week WKY and there was minimal response to NPY in either the SHR and WKY animals at 5 or 3 weeks. Neither PE nor NPY affected CHL in the 3‐week old animals of either strain. Thus, while PE elicited similar responses in the SHR and the WKY animals, the sensitivity to exogenous NPY became pronounced with age in the SHR. These data provide the first evidence that the development of hypertension in the SHR involves an upregulation of the NPY system.

Study of rotating permanent magnetic field to treat steroid-induced osteonecrosis of femoral head

Sixty New Zealand rabbit models with steroid-induced necrosis of femoral head were exposed to a rotating permanent magnetic field (RPMF) (group A1-2 h/d for one month and group A2-2 h/d for two months), and the changes of femoral head, blood viscosity, serum cholesterol, triglyceride, and pressure within the hip joint cavity were measured and statistically analysed compared to that of control group (B1 and B2) and sham group (C1 and C2). After RPMF treatment, the osteogenesis regeneration of the necrotic femoral head was markedly improved, as was shown by micro-CT. Blood viscosity, serum cholesterol, triglyceride, and pressure in the hip joint cavity were found significantly reduced. RPMF could affect various critical aspects in the course of femoral head necrosis, which will be a promising measure in the prevention and treatment of steroid-induced necrosis of femoral head, especially in the early stage.

Modelflow method versus continuous thermodilution technique for cardiac output measurement in liver transplant patients

In critically ill patients, cardiac output (CO) is used as a parameter for assessing hemodynamic status and efficacy of treatment. Continuous CO (CCO) could facilitate this assessment during general anesthesia. A new method of arterial pulse wave analysis has been introduced, which estimates beat to beat CO from arterial pressure via Modelflow. It remains uncertain how well this method performs in high output states. We analyzed the relationship between CCO and Modelflow computed from radial and femoral pressures (MFCORA, MFCOFA) during liver transplantation (LT). Methods: Measurements were performed in 100 liver transplant patients. Groups A had 36 patients, and group C had 64 patients with both groups composed of Child-Turcotte A, B and C patients Eighty patients had CCO ＜ 10 L/min (group D), and 20 patients had CCO ＞ 10 L/min (group E) during anhepatic phase. Results: CCO ranged from 5.0 to 15.4 L/min (MFCORA 3.2 to 10.7 L/min, MFCOFA 4.3 to 11.8 L/min). Bland-Altman analyses showed the limit of agreement of MFCORA (−1.5 to 5.2, bias = 1.9 L/min) and of MFCOFA (−2.6 to 4.4, bias = 0.9 L/min). CO measured by the two methods was significantly different in groups, except for MFCOFA in group C. In group D, bias was 1.5 L/min (SD 1.3 L/min) for MFCORA and 0.9 L/min for MFCOFA (SD 1.4 L/min). In group E, biases of 3.5 L/min and 2.4 L/min were obtained for MFCORA and MFCOFA, respectively. Conclusions: These results suggest that the group-average value of MFCO is not an accurate parameter for estimating CO during LT, with the exception of MFCOFA in groups C and D.

Arterial structure and function and environmental exposure to cadmium

Objectives: Few studies have addressed the effect of cadmium toxicity on arterial properties. Methods: We investigated the possible association of 24 h urinary cadmium excretion (an index of lifetime exposure)...

Arterial Structure and Function and Environmental Exposure to Cadmium

Objectives: Few studies have addressed the effect of cadmium toxicity on arterial properties. Methods: We investigated the possible association of 24 h urinary cadmium excretion (an index of lifetime exposure) with measures of arterial function in a randomly selected population sample (n= 557) from two rural areas with low and high environmental exposure to cadmium. Results: 24 h urinary cadmium excretion was significantly higher in the high compared with the low exposure group (p < 0.001). Even though systolic (p = 0.42), diastolic (p = 0.14) and mean arterial pressure (p = 0.68) did not differ between the high and low exposure groups, aortic pulse wave velocity (p = 0.008), brachial pulse pressure (p = 0.026) and femoral pulse pressure (p = 0.008) were significantly lower in the high exposure group. Additionally, femoral distensibility (p, 0.001) and compliance (p = 0.001) were significantly higher with high exposure. Across quartiles of 24 h urinary cadmium excretion (adjusted for sex and age), brachial (p for trend = 0.015) and femoral (p for trend= 0.018) pulse pressure significantly decreased and femoral distensibility (p for trend= 0.008) and compliance (p for trend= 0.007) significantly increased with higher cadmium excretion. After full adjustment, the partial regression coefficients confirmed these associations. Pulse wave velocity (beta = -0.79 +/- 0.27; p = 0.004) and carotid (beta = -4.20 +/- 1.51; p = 0.006), brachial (beta = -5.43 +/- 1.41; p = 0.001) and femoral (beta = -4.72 +/- 1.74; p = 0.007) pulse pressures correlated negatively, whereas femoral compliance (beta = 0.11 +/- 0.05; p = 0.016) and distensibility (beta = 1.70 +/- 0.70; p = 0.014) correlated positively with cadmium excretion. Conclusion: Increased cadmium body burden is associated with lower aortic pulse wave velocity, lower pulse pressure throughout the arterial system, and higher femoral distensibility.

Rationale, design, methods and baseline characteristics of the Asklepios Study

The Asklepios Study is a longitudinal population study focusing on the interplay between ageing, cardiovascular haemodynamics and inflammation in (preclinical) cardiovascular disease. The 2524 participants (1301 women) are a representative cohort of 35-55-year-old individuals, free from overt cardiovascular disease at study initiation, randomly sampled from the twinned Belgian communities of Erpe-Mere and Nieuwerkerken. Baseline examinations (all single-observer, single-device, single-site, single 2-year consecutive timeframe) include: questionnaires, conventional risk factors and biochemistry. Additional phenotypes under study include: (a) vascular structure and function: carotid and femoral atherosclerosis (intima-media thickness, plaque), arterial distension and pressure curves (brachial, carotid, femoral; wall-tracking and applanation tonometry); (b) cardiac structure and function. A novel aspect of the study is 'integrated' non-invasive biomechanical assessment of cardiac, arterial and ventriculovascular function through a combination of modeling, fundamental hydraulical measurements and system identification techniques. Integrated phenotypes result from combining at least two sets of curves (flow/pressure/distension). The value of this 'integrated' haemodynamic phenotype in the detection, prediction and prevention of clinical cardiovascular pathology (atherosclerosis progression, atherothrombosis, development of heart failure) will be tested. A second novel aspect is the systematic determination of peripheral blood leukocyte telomere length as a marker for biological ageing. During follow-up, baseline examinations will be repeated and the incidence of cardiovascular events will be monitored. Sex-specific baseline risk factor and biochemical data are provided in the current analyses. The primary aim is to build a combined dataset that will act as a tool to answer a cluster of questions about ageing, haemodynamics and the emergence of cardiovascular disease, especially the incidence of atherothrombotic events and the development of adverse haemodynamic profiles (arterial stiffening, heart failure). The study will reassess current risk factors and provide a long-term base for the detection of novel (epi)genetic and non-genetic risk factors and for more performant risk stratification modalities. Within these broader goals, a constant will be to strive towards more fundamental mechanistic-haemodynamic insights into cardiovascular disease processes.

Comparison between uncalibrated cardiac output using the femoral and radial arterial pressure waveform in critically ill patients

Cardiac output (CO) monitoring is often required to manage critically ill patients. Nominal values can be determined from analysis of arterial pressure waveforms. It is assumed that arterial waveforms from different arterial sites give similar CO values. The aim of this study was to compare the values of uncalibrated CO derived from simultaneous radial (COr) and femoral (COf) blood pressures.

Serum levels of ischemia-modified albumin in healthy volunteers after exercise-induced calf-muscle ischemia

Ischemia-modified albumin (IMA) is an emerging marker of ischemia. To investigate the applicability of IMA for the diagnosis of skeletal muscle ischemia, we examined IMA changes as measured by the albumin-cobalt binding test, in a group of healthy volunteers after standardized exercise-induced calf muscle ischemia. A total of 12 healthy volunteers underwent standardized exercise on a plantar flexion pedal. Ischemic conditions were achieved by inflating a femoral blood pressure cuff at incremental pressures of 0, 60, 90, 120 and 150 mm Hg. Calf muscle ischemia was identified by synchronous 31P magnetic resonance spectroscopy, measuring intracellular concentrations of phosphocreatine (PCr) and inorganic phosphate (Pi). In addition, IMA, serum albumin, lactate, troponin T (TnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at baseline and at 5, 10, 30, 360 and 720 min after cuff release. Magnetic resonance spectroscopy showed calf muscle ischemia in all participants upon exercise and cuff inflation. Circulating IMA concentrations increased significantly after cuff release (p=0.03) and returned to baseline within 30 min. While we found a significant negative correlation with albumin, there was no association of IMA levels with lactate or intracellular levels of PCr or Pi in samples obtained at baseline and post-ischemia. TnT and NT-proBNP remained within the normal range throughout the observation period in all participants. IMA may represent a clinical marker for skeletal muscle ischemia, although its lack of specificity requires careful clinical interpretation of data. The short period of IMA elevation after ischemic exercise requires standardized conditions for use as a diagnostic tool and hints at IMA applicability as a marker of prolonged or chronic ischemia.

Effect of Angiotensin II on the peripheral vasculature during rest low, mild, and heavy exercise workloads

INTRODUCTION: Exercise mediated increases in sympathetic activity leads to increased production of the non-adrenergic vasoconstrictor Angiotensin II (AngII). PURPOSE: To test the hypothesis that as exercise intensity increases AngII plays a greater role in the control of the peripheral vasculature. METHODS: We compared the vasoconstrictor responses before and after blockade of the Angiotensin type 1 receptor (AT1) with Valsartan (80mg) in healthy humans (n=5) during rest and knee-extensor exercise at ~40%, 60% and 80% of workmax. Neck suction (NS) stimuli were used to partially withdraw the arterial baroreflex mediated sympathetic activity. Ultrasound Doppler provided measurements of femoral blood flow (FBF) and blood pressures were used to calculate femoral vascular conductance (FVC). RESULTS: FVC was unchanged at rest and during the 40% and 60% exercise trials with Valsartan, however during 80% exercise with Valsartan FVC was increased by 17 ± 3% with Valsartan when compared to control exercise. NS elicited significant increases in FVC during rest and all 3 exercise trials. During 80% exercise NS mediated increases in FVC was further increased by 40 ± 7% with Valsartan when compared to control exercise. CONCLUSION: These data identify that as exercise intensity and duration increases AngII plays a greater percentage role in the control of the peripheral vasculature. Supported in part by NIH grant #HL-045547

Exercise‐induced inhibition of angiotensin II vasoconstriction in human thigh muscle

It is well established that metabolic inhibition of adrenergic vasoconstriction contributes to the maintenance of adequate perfusion to exercising skeletal muscle. However, little is known regarding nonadrenergic vasoconstriction during exercise. We tested the hypothesis that a non-adrenergic vasoconstrictor, angiotensin II (AngII), would be less sensitive to metabolic inhibition than an alpha1-agonist, phenylephrine (PE), in the exercising human thigh. In 11 healthy men, femoral blood flow (FBF, ultrasound Doppler and thermodilution) and blood pressure were evaluated during wide-ranging doses of intra-arterial (femoral) infusions of PE and AngII at rest and during two workloads of steady-state knee-extensor exercise (7 W and 27 W). At rest, the maximal decrease in femoral artery diameter (FAD) during AngII (9.0+/-0.2 to 8.4+/-0.4 mm) was markedly less than during PE (9.0+/-0.3 to 5.7+/-0.5 mm), whereas maximal reductions in FBF and femoral vascular conductance (FVC) were similar during AngII (FBF: -65+/-6 and FVC: -66+/-6%) and PE (-57+/-5 and -59+/-4%). During exercise, FAD was not changed by AngII, but moderately decreased by PE. The maximal reductions in FBF and FVC were blunted during exercise compared to rest for both AngII (7 W: -28+/-5 and -40+/-5%; 27 W: -15+/-4% and -29+/-5%) and PE (7 W: -30+/-4 and -37+/-6%; 27 W: -15+/-2 and -24+/-6%), with no significant differences between drugs. The major new findings are (1) an exercise-induced intensity-dependent metabolic attenuation of non-adrenergic vasoconstriction in the human leg; and (2) functional evidence that AngII-vasoconstriction is predominantly distal, whereas alpha1-vasoconstriction is proximal and distal within the muscle vascular bed of the human thigh.