Allometric scaling of mammalian blood pressure: A comment on White and Seymour (2014)

White and Seymour examined the scaling of central arterial blood pressure against body mass in mammals ranging in size from a 30 g mouse to a 4080 kg elephant. Exponents in power functions fitted to each of three datasets (systolic, diastolic, and mean arterial pressure) were reported to be significantly greater than zero and indistinguishable from 0.33. The first of these outcomes would indicate that blood pressure increases with body size, whereas the second is consistent with the heart working against gravity to move blood to the head. Taken together, these results seemingly refute the notion that the cephalic circulation functions as an energy‐neutral siphon. However, the main findings by White and Seymour were presented in the form of graphs that distorted the relationships between the variables of interest. I use simple graphics to show that the data were unsuited from the outset for use in allometric analyses and that conclusions of the investigation are not well supported.     

Body height and blood pressure regulation in humans during anti-orthostatic tilting

The hypothesis was tested that the cardiovascular changes during an upper body anti-orthostatic maneuver in humans are more pronounced in tall than in short individuals, because of the larger intravascular hydrostatic pressure gradients. In 34 males and 41 females [20-30 yr, body height (BH) = 147-206 cm], inter-individual multiple linear regression analyses adjusted for gender and body weight were conducted between changes in cardiovascular variables versus BH during tilting of the upper body from vertical to horizontal while keeping the legs horizontal. In all the subjects, tilting induced increases in stroke volume and arterial pulse pressure and a decrease in heart rate, which each correlated significantly with BH. In males (n = 51, BH = 163-206 cm), 24-h ambulatory mean arterial pressure increased significantly with BH (P = 0.004, r = 0.40, α = 0.15 mmHg/cm) so that systolic/diastolic blood pressure increased by 2/2 mmHg per 15 cm increase in BH. There was no significant correlation between mean arterial pressure and BH in females (n = 53, BH = 147-193 cm). In conclusion, a larger BH induces larger cardiovascular changes during anti-orthostatic tilting, and in males 24-h ambulatory mean arterial pressure increases with BH. The lack of a mean arterial pressure to BH correlation in females is probably because of their lower BH and greater variability in blood pressure.     

Intraspecific temperature dependence of the scaling of metabolic rate with body mass in fishes and its ecological implications

Metabolism constitutes a fundamental property of all organisms. Metabolic rate is commonly described to scale as a power function of body size and exponentially with temperature, thereby treating the effects of body size and temperature independently. Mounting evidence shows that the scaling of metabolic rate with body mass itself depends on temperature. Across‐species analyses in fishes suggest that the mass‐scaling exponent decreases with increasing temperature. However, whether this relationship holds at the within‐species level has rarely been tested. Here, we re‐analyse data on the metabolic rates of four freshwater fish species, two coregonids and two cyprinids, that cover wide ranges of body masses and their naturally experienced temperatures. We show that the standard metabolic rate of the coregonids is best fit when accounting for a linear temperature dependence of the scaling of metabolic rate with body mass, whereas a constant mass‐scaling exponent is supported in case of the cyprinids. Our study shows that phenotypic responses to temperature can result in temperature‐dependent scaling relationships at the species level and that these responses differ between taxa. Together with previous findings, these results indicate that evolutionarily adaptive and phenotypically plastic responses to temperature affect the scaling of metabolic rate with body mass in fishes.     

Sample size and mass range effects on the allometric exponent of basal metabolic rate

The controversial relationship between body mass and basal metabolic rate in animals revolves around two questions: what is the allometric scaling exponent and what is the functional basis for it? For mammals, the first question could be resolved if measurements from all 4600 extant species were available, but this study shows that data for only 150 species, spanning three to four orders of magnitude variation in body mass, are sufficient to accurately determine the exponent. Because the currently available data set includes about 600 species that vary over five orders of magnitude in body size, further increases in sample size are unlikely to change the estimate of the scaling exponent.     

Hemodynamic effects of blood loss during a passive response to a stressor in the conscious rabbit

In the conscious rabbit, exposure to an air jet stressor increases arterial pressure, heart rate, and cardiac output. During hemorrhage, air jet exposure extends the blood loss necessary to produce hypotension. It is possible that this enhanced defense of arterial pressure is a general characteristic of stressors. However, some stressors such as oscillation (OSC), although they increase arterial pressure, do not change heart rate or cardiac output. The cardiovascular changes during OSC resemble those seen during freezing behavior. In the present study, our hypothesis was that, unlike air jet, OSC would not affect defense of arterial blood pressure during blood loss. Male New Zealand White rabbits were chronically prepared with arterial and venous catheters and Doppler flow probes. We removed venous blood until mean arterial pressure decreased to 40 mmHg. We repeated the experiment in each rabbit on separate days in the presence and absence (SHAM) of OSC. Compared with SHAM, OSC increased arterial pressure 14 +/- 1 mmHg, central venous pressure 3.3 +/- 0.4 mmHg, and hindquarter blood flow 34 +/- 4% while decreasing mesenteric conductance 32 +/- 3% and not changing heart rate or cardiac output. During normotensive hemorrhage, OSC enhanced hindquarter and renal vasoconstriction. Contrary to our hypothesis, OSC (23.5 +/- 0.6 ml/kg) increased the blood loss necessary to produce hypotension compared with SHAM (16.8 +/- 0.6 ml/kg). In nine rabbits, OSC prevented hypotension even after a blood loss of 27 ml/kg. Thus a stressful stimulus that resulted in cardiovascular changes similar to those seen during freezing behavior enhanced defense of arterial pressure during hemorrhage.     

Testing metabolic scaling theory using intraspecific allometries in Antarctic microarthropods

Quantitative scaling relationships among body mass, temperature and metabolic rate of organisms are still controversial, while resolution may be further complicated through the use of different and possibly inappropriate approaches to statistical analysis. We propose the application of a modelling strategy based on the theoretical approach of Akaike's information criteria and non‐linear model fitting (nlm). Accordingly, we collated and modelled available data at intraspecific level on the individual standard metabolic rate of Antarctic microarthropods as a function of body mass (M), temperature (T), species identity (S) and high rank taxa to which species belong (G) and tested predictions from metabolic scaling theory (mass‐metabolism allometric exponent b = 0.75, activation energy range 0.2–1.2 eV). We also performed allometric analysis based on logarithmic transformations (lm). Conclusions from lm and nlm approaches were different. Best‐supported models from lm incorporated T, M and S. The estimates of the allometric scaling exponent linking body mass and metabolic rate resulted in a value of 0.696 ± 0.105 (mean ± 95% CI). In contrast, the four best‐supported nlm models suggested that both the scaling exponent and activation energy significantly vary across the high rank taxa (Collembola, Cryptostigmata, Mesostigmata and Prostigmata) to which species belong, with mean values of b ranging from about 0.6 to 0.8. We therefore reached two conclusions: 1, published analyses of arthropod metabolism based on logarithmic data may be biased by data transformation; 2, non‐linear models applied to Antarctic microarthropod metabolic rate suggest that intraspecific scaling of standard metabolic rate in Antarctic microarthropods is highly variable and can be characterised by scaling exponents that greatly vary within taxa, which may have biased previous interspecific comparisons that neglected intraspecific variability.     

Baroreflex control of muscle sympathetic nerve activity during skin surface cooling.

Skin surface cooling improves orthostatic tolerance through a yet to be identified mechanism. One possibility is that skin surface cooling increases the gain of baroreflex control of efferent responses contributing to the maintenance of blood pressure. To test this hypothesis, muscle sympathetic nerve activity (MSNA), arterial blood pressure, and heart rate were recorded in nine healthy subjects during both normothermic and skin surface cooling conditions, while baroreflex control of MSNA and heart rate were assessed during rapid pharmacologically induced changes in arterial blood pressure. Skin surface cooling decreased mean skin temperature (34.9 +/- 0.2 to 29.8 +/- 0.6 degrees C; P < 0.001) and increased mean arterial blood pressure (85 +/- 2 to 93 +/- 3 mmHg; P < 0.001) without changing MSNA (P = 0.47) or heart rate (P = 0.21). The slope of the relationship between MSNA and diastolic blood pressure during skin surface cooling (-3.54 +/- 0.29 units.beat(-1).mmHg(-1)) was not significantly different from normothermic conditions (-2.94 +/- 0.21 units.beat(-1).mmHg(-1); P = 0.19). The slope depicting baroreflex control of heart rate was also not altered by skin surface cooling. However, skin surface cooling shifted the "operating point" of both baroreflex curves to high arterial blood pressures (i.e., rightward shift). Resetting baroreflex curves to higher pressure might contribute to the elevations in orthostatic tolerance associated with skin surface cooling.     

Dynamic autoregulation of cutaneous circulation: differential control in glabrous versus nonglabrous skin

The purpose of this project was to test the hypothesis that, independent of neural control, glabrous and nonglabrous cutaneous vasculature is capable of autoregulating blood flow. In 10 subjects, spectral and transfer function analyses of arterial pressure and skin blood flow (laser-Doppler flowmetry) from glabrous (palm) and nonglabrous (forearm) regions were performed under three conditions: baseline, ganglionic blockade via intravenous trimethaphan administration, and trimethaphan plus oscillatory lower body negative pressure (LBNP; -5 to -10 mmHg) from 0.05 to 0.07 Hz. Oscillatory LBNP was applied to regenerate mean arterial pressure variability that was abolished by ganglionic blockade. Ganglionic blockade was verified by an absence of a heart rate response to a Valsalva maneuver. Spectral power and transfer function gain between blood pressure and skin blood flow were calculated in this oscillatory frequency range (0.05-0.07 Hz). Within this frequency range, ganglionic blockade significantly decreased spectral power of blood flow in both the forearm and palm, whereas regeneration of arterial blood pressure oscillations significantly increased spectral power of forearm blood flow but not palm blood flow. During oscillatory LBNP, transfer function gain between blood pressure and skin blood flow was significantly elevated at the forearm (0.28 +/- 0.03 to 0.53 +/- 0.02 flux units/mmHg; P < 0.05) but was reduced at the palm (4.7 +/- 0.5 to 1.2 +/- 0.1 flux units/mmHg; P < 0.05). These data show that independent of neural control of blood flow, glabrous skin has the ability to buffer blood pressure oscillations and demonstrates a degree of dynamic autoregulation. Conversely, these data suggest that nonglabrous skin has diminished dynamic autoregulatory capabilities.     

Baroreceptor influence on a spinal cardiovascular reflex

A stretch of the walls of the thoracic aorta, performed in vagotomized cats without obstructing aortic flow, induces increases in heart rate, myocardial contractility, and arterial pressure. These reflex responses are still present after high spinal section. Cats under chloralose-urethane anesthesia were vagotomized and one carotid sinus was isolated and perfused with arterial blood at constant flow. The contralateral carotid sinus nerve and both aortic nerves were sectioned. A stretch of the walls of the thoracic aorta between the 7th and 10th intercostal arteries induced a reflex increase in mean arterial pressure 29 +/- 2 mmHg (mean +/- SE). Stepwise increases of carotid sinus pressure (CSP) or electrical stimulation of the carotid sinus nerve induced stepwise decreases of this reflex response. At maximal baroreceptor stimulation (CSP 212 +/- 9 mmHg) the reflex response to aortic stretch was reduced by 42%. These experiments show that this spinal cardiovascular reflex is at least partially under the inhibitory control of the baroreceptor input.     

PHYLOGENETICALLY INFORMED ANALYSIS OF THE ALLOMETRY OF MAMMALIAN BASAL METABOLIC RATE SUPPORTS NEITHER GEOMETRIC NOR QUARTER-POWER SCALING

The form of the relationship between the basal metabolic rate (BMR) and body mass (M) of mammals has been at issue for almost seven decades, with debate focusing on the value of the scaling exponent ( b , where BMR ∝ M^b ) and the relative merits of b = 0.67 (geometric scaling) and b = 0.75 (quarter-power scaling). However, most analyses are not phylogenetically informed (PI) and therefore fail to account for the shared evolutionary history of the species they consider. Here, we reanalyze the most rigorously selected and comprehensive mammalian BMR dataset presently available, and investigate the effects of data selection and phylogenetic method (phylogenetic generalized least squares and independent contrasts) on estimation of the scaling exponent relating mammalian BMR to M. Contrary to the results of a non-PI analysis of these data, which found an exponent of 0.67–0.69, we find that most of the PI scaling exponents are significantly different from both 0.67 and 0.75. Similarly, the scaling exponents differ between lineages, and these exponents are also often different from 0.67 or 0.75. Thus, we conclude that no single value of b adequately characterizes the allometric relationship between body mass and BMR.     

Strength training reduces arterial blood pressure but not sympathetic neural activity in young normotensive subjects.

The effects of resistance training on arterial blood pressure and muscle sympathetic nerve activity (MSNA) at rest have not been established. Although endurance training is commonly recommended to lower arterial blood pressure, it is not known whether similar adaptations occur with resistance training. Therefore, we tested the hypothesis that whole body resistance training reduces arterial blood pressure at rest, with concomitant reductions in MSNA. Twelve young [21 +/- 0.3 (SE) yr] subjects underwent a program of whole body resistance training 3 days/wk for 8 wk. Resting arterial blood pressure (n = 12; automated sphygmomanometer) and MSNA (n = 8; peroneal nerve microneurography) were measured during a 5-min period of supine rest before and after exercise training. Thirteen additional young (21 +/- 0.8 yr) subjects served as controls. Resistance training significantly increased one-repetition maximum values in all trained muscle groups (P < 0.001), and it significantly decreased systolic (130 +/- 3 to 121 +/- 2 mmHg; P = 0.01), diastolic (69 +/- 3 to 61 +/- 2 mmHg; P = 0.04), and mean (89 +/- 2 to 81 +/- 2 mmHg; P = 0.01) arterial blood pressures at rest. Resistance training did not affect MSNA or heart rate. Arterial blood pressures and MSNA were unchanged, but heart rate increased after 8 wk of relative inactivity for subjects in the control group (61 +/- 2 to 67 +/- 3 beats/min; P = 0.01). These results indicate that whole body resistance exercise training might decrease the risk for development of cardiovascular disease by lowering arterial blood pressure but that reductions of pressure are not coupled to resistance exercise-induced decreases of sympathetic tone.     

Muscle sympathetic nerve activity during lower body negative pressure is accentuated in heat-stressed humans.

The purpose of this project was to test the hypothesis that increases in muscle sympathetic nerve activity (MSNA) during an orthostatic challenge is attenuated in heat-stressed individuals. To accomplish this objective, MSNA was measured during graded lower body negative pressure (LBNP) in nine subjects under normothermic and heat-stressed conditions. Progressive LBNP was applied at -3, -6, -9, -12, -15, -18, -21, and -40 mmHg for 2 min per stage. Whole body heating caused significant increases in sublingual temperature, skin blood flow, sweat rate, heart rate, and MSNA (all P < 0.05) but not in mean arterial blood pressure (P > 0.05). Progressive LBNP induced significant increases in MSNA in both thermal conditions. However, during the heat stress trial, increases in MSNA at LBNP levels higher than -9 mmHg were greater compared with during the same LBNP levels in normothermia (all P < 0.05). These data suggest that the increase in MSNA to orthostatic stress is not attenuated but rather accentuated in heat-stressed humans.     

Naturally occurring hypertension in New World nonhuman primates: Potential role of the perifornical hypothalamus

Hypertension is a prominent underlying factor in the genesis of cardiovascular-related morbidity and mortality. A major impediment to the investigation into the causes of the disease is the paucity of naturally occurring animal models of the disease. There is evidence that some species of New World primates spontaneously become hypertensive. We used chronically implanted pressure transducers to assess normally occurring blood pressure and heart rate levels at rest and during routine laboratory procedures in a group of one of these New World primates (Aotus sp.). Resting mean arterial pressure ranged from 72 to 130 mmHg. Three animals were judged to have resting mean arterial pressure levels in the hypertensive range (> or =110 mmHg). In all of the animals, pressor responses to routine laboratory events were exaggerated (average highest mean pressure during 1 min from any session was 97-196 mmHg). Subsequently, the region of the perifornical/lateral hypothalamus known to produce elevated blood pressure and heart rate responses to electrical stimulation was removed, and the blood pressure responses to the laboratory routines were significantly decreased and, in some cases, eliminated. Control lesions in nearby tissue had no effect on these responses. This region may play a critical role in initiating or exacerbating cardiovascular responses that contribute to the development of essential hypertension.     

Ontogenetic and interspecific scaling of consumption in insects

The uptake of resources from the environment is a basic feature of all life. Consumption rate has been found to scale with body size with an exponent close to unity across diverse organisms. However, past analyses have ignored the important distinction between ontogenetic and interspecific size comparisons. Using principles of dynamic energy budget theory, we present a mechanistic model for the body mass scaling of consumption, which separates interspecific size effects from ontogenetic size effects. Our model predicts uptake to scale with surface‐area (mass^2/3) during ontogenetic growth but more quickly (between mass^3/4 and mass¹) for interspecific comparisons. Available data for 41 insect species on consumption and assimilation during ontogeny provides strong empirical support for our theoretical predictions. Specifically, consumption rate scaled interspecifically with an exponent close to unity (0.89) but during ontogenetic growth scaled more slowly with an exponent of 0.70. Assimilation rate (consumption minus defecation) through ontogeny scaled more slowly than consumption due to a decrease in assimilation efficiency as insects grow. Our results highlight how body size imposes different constraints on metabolism depending on whether the size comparison is ontogenetic or inter‐specific. Synthesis One of the most robust patterns in biology is the effect of body size on metabolism – a relationship that underlies the rapidly emerging field of metabolic ecology. However, the precise energetic constraints imposed by body size have been notoriously difficult to entangle. Here we show that the constraints imposed on metabolism by body size are different depending on whether the size comparison is ontogenetic or interspecific. Using a single unifying theory of animal metabolism and a newly compiled data set on insect consumption and assimilation rates, we show that interspecific comparisons generally lead to the estimation of higher scaling exponents compared with ontogenetic comparisons. Our results help to explain large variation in estimated metabolic scaling exponents and will encourage future studies in metabolic ecology to make the important distinction between ontogenetic and evolutionary size changes.     

Role of the area postrema in angiotensin II modulation of baroreflex control of heart rate in conscious mice

This study reports the effects of angiotensin II (ANG II), arginine vasopression (AVP), phenylephrine (PE), and sodium nitroprusside (SNP) on baroreflex control of heart rate in the presence and absence of the area postrema (AP) in conscious mice. In intact, sham-lesioned mice, baroreflex-induced decreases in heart rate due to increases in arterial pressure with intravenous infusions of ANG II were significantly less than those observed with similar increases in arterial pressure with PE (slope: -3.0 +/- 0.9 vs. -8.1 +/- 1.5 beats x min(-1) x mmHg(-1)). Baroreflex-induced decreases in heart rate due to increases in arterial pressure with intravenous infusions of AVP were the same as those observed with PE in sham animals (slope: -5.8 +/- 0.7 vs. -8.1 +/- 1.5 beats x min(-1) x mmHg(-1)). After the AP was lesioned, the slope of baroreflex inhibition of heart rate was the same whether pressure was increased with ANG II, AVP, or PE. The slope of the baroreflex-induced increases in heart rate due to decreases in arterial blood pressure with SNP were the same in sham- and AP-lesioned animals. These results indicate that, similar to other species, in mice the ability of ANG II to acutely reset baroreflex control of heart rate is dependent on an intact AP.     

Effects of airway pressure on bronchial blood flow

We studied the effects of increased airway pressure caused by increasing levels of positive end-expiratory pressure (PEEP) on bronchial arterial pressure-flow relationships. In eight alpha-chloralose-anesthetized mechanically ventilated sheep (23-27 kg), the common bronchial artery, the bronchial branch of the bronchoesophageal artery, was cannulated and perfused with a pump. The control bronchial blood flow (avg 12 +/- 1 ml/min or 0.48 ml X min-1 X kg-1) was set to maintain mean bronchial arterial pressure equal to systemic blood pressure. Pressure-flow curves of the bronchial circulation were measured by making step changes in bronchial blood flow, and changes in these curves were analyzed with measurements of the pressure at zero flow and the slope of the linearized curve. The zero-flow pressure represents the effective downstream pressure, and the slope represents the resistance through the bronchial vasculature. At a constant bronchial arterial pressure of 100 mmHg, an 8 mmHg increase in mean airway pressure caused a 40% reduction in bronchial blood flow. Under constant flow conditions, increases in mean airway pressure with the application of PEEP caused substantial increases in bronchial arterial pressure, averaging 4.6 mmHg for every millimeters of mercury increase in mean airway pressure. However, bronchial arterial pressure at zero flow increased approximately one-for-one with increases in mean airway pressure. Thus the acute sensitivity of the bronchial artery to changes in mean airway pressure results primarily from changes in bronchovascular resistance and not downstream pressure.     

Leg crossing improves orthostatic tolerance in healthy subjects: a placebo-controlled crossover study

Vasovagal syncope is the most common cause of transient loss of consciousness, and recurrent vasovagal fainting has a profound impact on quality of life. Physical countermaneuvers are applied as a means of tertiary prevention but have so far only proven useful at the onset of a faint. This placebo-controlled crossover study tested the hypothesis that leg crossing increases orthostatic tolerance. Nine na?ve healthy subjects [6 females, median age 25 yr (range 20-41 yr), mean body mass index 23 (SD 2)] were subjected to passive head-up tilt combined with a graded lower body negative pressure challenge (20, 40, and 60 mmHg) determining orthostatic tolerance thrice, in randomized order: 1) control, 2) with leg crossing, and 3) with oral placebo. Blood pressure (Finometer), heart rate, and changes in thoracic blood volume (impedance), stroke volume, and cardiac output (Modelflow) were followed during orthostatic stress. Primary outcome was time to presyncope (systolic blood pressure /=140 beats/min). With leg crossing, orthostatic tolerance increased from 26 +/- 2 to 34 +/- 2 min (placebo 23 +/- 3 min, P < 0.001). During leg crossing, mean arterial pressure (81 vs. 81 mmHg) and cardiac output (95 vs. 94% supine) remained unchanged; heart rate increase was lower (13 vs. 18 beats/min, P < 0.05); stroke volume was higher (79 vs. 74% supine, P < 0.05); and there was a trend toward lower thoracic impedance. Leg crossing increases orthostatic tolerance in healthy human subjects. As a measure of prevention, it is a worthwhile addition to the management of vasovagal syncope.     

Autonomic dysreflexia during sperm retrieval in spinal cord injury: influence of lesion level and sildenafil citrate.

Autonomic dysreflexia (AD) can occur during penile vibratory stimulation in men with spinal cord injury, but this is variable, and the association with lesion level is unclear. The purpose of this study was to characterize the cardiovascular responses to penile vibratory stimulation in men with spinal cord injury. We hypothesized that those with cervical injuries would demonstrate a greater degree of AD compared with men with thoracic injuries. We also questioned whether the rise in blood pressure could be attenuated by sildenafil citrate. Participants were classified as having cervical (n = 8) or thoracic (n = 5) injuries. While in a supine position, subjects were instrumented with an ECG, and arterial blood pressure was determined beat by beat. Subjects reported to the laboratory twice and received an oral dose of sildenafil citrate (25-100 mg) or no medication. Penile vibratory stimulation was performed using a handheld vibrator to the point of ejaculation. At ejaculation during the nonmedicated trials, the cervical group had a significant decrease in heart rate (-5-10 beats/min) and increase in mean arterial blood pressure (+70-90 mmHg) relative to resting conditions, whereas the thoracic group had significant increases in both heart rate (+8-15 beats/min) and mean arterial pressure (+25-30 mmHg). Sildenafil citrate had no effect on the change in heart rate or mean arterial pressure in either group. In summary, men with cervical injuries had more pronounced AD during penile vibratory stimulation than men with thoracic injuries. Administration of sildenafil citrate had no effect on heart rate or blood pressure during penile vibratory stimulation in men with spinal cord injury.     

下体负压对家兔血液动力学的影响

观察了家兔在-20、-40、-60mmHg下体负压下心输出量、心搏量、心率、血压以及心电图、脑电图、视网膜电图的变化。实验结果表明:心搏量与心输出量明显减少,在-60mmHg下作用10分钟两者可下降到负压前对照值的15％。心率大多数加快,以代偿心输出量的下降。如出现持续性心率过缓和心律不齐,标志代偿失调。收缩压、舒张压、平均动脉压、脉压均呈规律性下降。根据血压反应可将动物分为耐力良好、尚好、较差三种类型。心电图变化主要表现为冠脉供血不足,心肌缺氧特征,并伴有高尖状P波。脑电图出现缺氧性慢波、波幅降低。视网膜电图的b波波幅逐渐下降,持续期缩短,80％以上有b负波,这些变化可能与脑部及视网膜供血不足有关。     

Reflex control of vascular capacitance during hypoxia, hypercapnia, or hypoxic hypercapnia

We tested the hypothesis that the changes in venous tone induced by changes in arterial blood oxygen or carbon dioxide require intact cardiovascular reflexes. Mongrel dogs were anesthetized with sodium pentobarbital and paralyzed with veruronium bromide. Cardiac output and central blood volume were measured by indocyanine green dilution. Mean circulatory filling pressure, an index of venous tone at constant blood volume, was estimated from the central venous pressure during transient electrical fibrillation of the heart. With intact reflexes, hypoxia (arterial PaO2 = 38 mmHg), hypercapnia (PaCO2 = 72 mmHg), or hypoxic hypercapnia (PaO2 = 41; PaCO2 = 69 mmHg) (1 mmHg = 133.32 Pa) significantly increased the mean circulatory filling pressure and cardiac output. Hypoxia, but not normoxic hypercapnia, increased the mean systemic arterial pressure and maintained the control level of total peripheral resistance. With reflexes blocked with hexamethonium and atropine, systemic arterial pressure supported with a constant infusion of norepinephrine, and the mean circulatory filling pressure restored toward control with 5 mL/kg blood, each experimental gas mixture caused a decrease in total peripheral resistance and arterial pressure, while the mean circulatory filling pressure and cardiac output were unchanged or increased slightly. We conclude that hypoxia, hypercapnia, and hypoxic hypercapnia have little direct influence on vascular capacitance, but with reflexes intact, there is a significant reflex increase in mean circulatory filling pressure.