Role of splanchnic constriction in governing the hemodynamic responses to gravitational stress in conscious dogs.

Octreotide is a somatostatin analog that constricts the splanchnic circulation, thereby improving orthostatic tolerance. We tested the hypotheses that octreotide improves orthostatic tolerance by 1)increasing cardiac filling (right atrial) pressure via reductions in vascular capacity; 2) by causing an upward (i.e., cranial) shift of the hydrostatic indifferent point; and 3) by increasing arterial pressure via a reduction in total vascular conductance. Studies were carried out in acepromazine-sedated, hexamethonium-treated atrioventricular-blocked conscious dogs lightly restrained in lateral recumbency. Beat-by-beat cardiac output was held constant via computer-controlled ventricular pacing at rest and during 30 s of 30° head-up tilt. Octreotide (1.5 µg/kg iv) raised right atrial pressure by 0.5 mmHg and raised mean arterial pressure by 11 mmHg by reducing total vascular conductance (all P < 0.05). Right atrial pressure fell by a similar amount in response to tilting before and after octreotide, thus there was no difference in location of the hydrostatic indifferent point. These data indicate that octreotide improves orthostatic tolerance by decreasing total vascular conductance and by increasing cardiac filling pressure via a reduction in unstressed vascular volume and not by eliciting a cranial shift of the location of the hydrostatic indifferent point.

Role of sympathetic responses on the hemodynamic consequences of rapid changes in posture in humans.

Tolerance to +G(z) gravitational stress is reduced when +G(z) stress is preceded by exposure to hypogravity (fractional, 0, or negative G(z)). For example, there is an exaggerated fall in eye-level arterial pressure (ELAP) early on during +G(z) stress (head-up tilt; HUT) when this stress is immediately preceded by -G(z) stress (head-down tilt; HDT), termed the "push-pull effect." The aim of the present study was to test the hypothesis that sympathetic responses contribute to the push-pull effect. Young, healthy subjects (n = 7 males and 3 females) were subjected to 30 s of 30 degrees HUT from a horizontal position and to 30 s of 30 degrees HUT when HUT was immediately preceded by 20 s of -15 degrees HDT. Four bouts of HDT-HUT were alternated between five bouts of HUT in a counterbalanced design, and 1 min was allowed for recovery between tilts. This protocol was repeated during clonidine administration (2.5 microg/kg bolus over 30 min and then continuously at 0.36 microg x kg(-1) x h(-1)). Clonidine blunted the vasomotor responses to tilting, and this led to exaggerated changes in arterial pressure. Clonidine exerted little specific influence on the push-pull effect. Thus sympathetic responses appear neither to contribute to, nor protect against, the push-pull effect for the rate and duration of tilting imposed in the present study.

Retrograde arterial leg blood flow during tilt-back from a head-up posture: importance of capacitive flows when arterial pressure changes.

The windkessel function of the arterial system converts the intermittent action of the heart into more continuous microcirculatory blood flow during diastole via the return of elastic energy stored in the walls of the arteries during systole. Might the same phenomenon occur regionally within the arterial system during tilting owing to regional differences in local arterial pressure imposed by gravity? We sought to test the hypothesis that during tilt-back from a head-up posture, the return of stored elastic energy in leg arteries would work to slow, or perhaps transiently reverse, the flow of blood in the femoral artery. Femoral artery blood flow and arterial pressure were recorded during tilt back from a 30 degrees head-up posture to supine (approximately 0.5 G) in young, healthy subjects (n = 7 males and 3 females) before and during clonidine infusion. During control (no drug) conditions femoral artery blood flow ceased for an entire heart beat during tilt-back. During clonidine infusion femoral artery blood flow reversed for at least one entire heart beat during tilt-back, i.e., blood flow in the retrograde direction in the femoral artery from the leg into the abdomen. Thus substantial capacitive effects of tilting on leg blood flow occur in humans during mild changes in posture.

Frequency response characteristics of whole body autoregulation of blood flow in rats.

Previously, we demonstrated that very low-frequency (VLF) blood pressure variability (BPV) depends on voltage-gated L-type Ca(2+)-channels, suggesting that autoregulation of blood flow and/or myogenic vascular function significantly contributes to VLF BPV. To further substantiate this possibility, we tested the hypothesis that the frequency response characteristic of whole body autoregulation of blood flow is consistent with the frequency range of VLF BPV (0.02-0.2 Hz) in rats. In anesthetized rats (n = 11), BPV (0.016-0.5 Hz) was induced by computer-regulated cardiac pacing while blood pressure, heart rate, and cardiac output (CO) were recorded during control conditions (NaCl, 1 ml/h iv) and during alpha(1)-adrenergic receptor stimulation (phenylephrine, 1 mg.ml(-1).h(-1) iv) that has been reported to facilitate myogenic vascular function. Baroreceptor-heart rate reflex responses were elicited to confirm a functional baroreflex despite anesthesia. During control conditions, transfer function analyses between mean arterial pressure (MAP) and CO, and between MAP and total vascular conductance (CO/MAP) indicated autoregulation of blood flow at 0.016 Hz, passive vascular responses between 0.033 and 0.2 Hz, and vascular responses compatible with baroreflex-mediated mechanisms at 0.333 and 0.5 Hz. Stimulation of alpha(1)-adrenergic receptors extended the frequency range of autoregulation of blood flow to frequencies up to 0.033 Hz. In conclusion, depending on sympathetic vascular tone, whole body autoregulation of blood flow operates most effectively at frequencies below 0.05 Hz. This frequency range overlaps with the lower end of the frequency band of VLF BPV in rats. Baroreceptor reflex-like mechanisms contribute to LF (0.2-0.6 Hz) but not VLF BPV-induced vascular responses.

Myogenic origin of the hypotension induced by rapid changes in posture in awake dogs following autonomic blockade.

The "push-pull" effect denotes the reduced tolerance to +G(z) (hypergravity) when +G(z) stress is preceded by exposure to hypogravity, i.e., fractional, zero, or negative G(z). The purpose of this study was to test the hypothesis that an exaggerated, myogenically mediated rise in leg vascular conductance contributes to the push-pull effect, using heart level arterial blood pressure as a measure of G tolerance. The approach was to impose control (30 s of 30 degrees head-up tilt) and push-pull (30 s of 30 degrees head-up tilt immediately preceded by 10 s of -15 degrees head-down tilt) gravitational stress after administration of hexamethonium (5 mg/kg) to inhibit autonomic ganglionic neurotransmission in seven dogs. Cardiac output or thigh level arterial pressure (myogenic stimulus) was maintained constant by computer-controlled ventricular pacing. The animals were sedated with acepromazine and lightly restrained in lateral recumbency on a tilt table. Following the onset of head-up tilt, the magnitude of the fall in heart level arterial pressure from baseline was -11.6 +/- 2.9 and -17.1 +/- 2.2 mmHg for the control and push-pull trials, respectively (P < 0.05), when cardiac output was maintained constant. Over 40% of the exaggerated fall in heart level arterial pressure was attributable to an exaggerated rise in hindlimb vascular conductance (P < 0.05). Maintaining thigh level arterial pressure constant abolished the exaggerated rise in hindlimb blood flow. Thus a push-pull effect largely attributable to a myogenically induced rise in leg vascular conductance occurs when autonomic function is inhibited.

Very low frequency blood pressure variability is modulated by myogenic vascular function and is reduced in stroke-prone rats.

BACKGROUND: Cerebrovascular myogenic function, which protects the brain from hemorrhagic stroke, is impaired in stroke-prone spontaneously hypertensive rats. Furthermore, myogenic function contributes to very low frequency blood pressure variability and dynamic autoregulation of cerebral blood flow is most effective at very low frequency in rats. Therefore, we hypothesized that very low frequency blood pressure variability is reduced in stroke-prone spontaneously hypertensive rats compared with stroke-resistant spontaneously hypertensive rats. In addition, we investigated if myogenic function also contributes to very low frequency blood pressure variability in conscious dogs. METHODS: In 8-week-old normotensive Wistar-Kyoto rats, 8-week-old and 15-week-old stroke-prone spontaneously hypertensive rats and stroke-resistant spontaneously hypertensive rats, and dogs, blood pressure variability was studied during control conditions, inhibition of myogenic function (nifedipine) and hypotension induced by sodium nitroprusside. In dogs, transfer function analysis between blood pressure and total peripheral resistance was performed to study the contribution of myogenic function to blood pressure variability. RESULTS: Inhibition of myogenic function, but not hypotension induced by sodium nitroprusside, significantly reduced very low frequency variability of systolic blood pressure (rats: 0.02-0.2 Hz; dogs: 0.02-0.075 Hz) in conscious rats and dogs. In dogs, the gain of the transfer function was high (0.28 +/- 0.04 min/l) in the very low frequency band and was decreased to 0.11 +/- 0.01 min/l (P < 0.05) by nifedipine but not by sodium nitroprusside (0.26 +/- 0.02 min/l). Very low frequency blood pressure variability was significantly smaller in stroke-prone spontaneously hypertensive rats than in stroke-resistant spontaneously hypertensive rats (8 weeks of age: 7.8 +/- 1.1 vs. 13.1 +/- 2.2 mmHg; P < 0.05; 15 weeks of age: 7.1 +/- 1.2 vs. 16.5 +/- 3.6 mmHg; P < 0.05). CONCLUSION: Myogenic function affects very low frequency blood pressure variability in conscious rats and dogs. The smaller very low frequency blood pressure variability in stroke-prone spontaneously hypertensive rats compared with stroke-resistant spontaneously hypertensive rats suggests that impaired cerebrovascular myogenic function is reflected in reduced very low frequency blood pressure variability.

Hemodynamic consequences of rapid changes in posture in humans.

Tolerance to +G(z) gravitational stress is reduced when +G(z) stress is preceded by exposure to hypogravity (fraction, 0, or negative G(z)). For example, there is an exaggerated fall in eye-level arterial pressure (ELAP) early on during +G(z) stress (head-up tilt; HUT) when this stress is immediately preceded by -G(z) stress (head-down tilt; HDT). The aims of the present study were to characterize the hemodynamic consequences of brief HDT on subsequent HUT and to test the hypothesis that an elevation in leg vascular conductance induced by -G(z) stress contributes to the exaggerated fall in ELAP. Young healthy subjects (n = 3 men and 4 women) were subjected to 30 s of 30 degrees HUT from a horizontal position and to 30 s of 30 degrees HUT when HUT was immediately preceded by 20 s of -15 degrees HDT. Four bouts of HDT-HUT were alternated between five bouts of HUT in a counterbalanced designed to minimize possible time effects of repeated exposure to gravitational stress. One minute was allowed for recovery between tilts. Brief exposure to HDT elicited an exaggerated fall in ELAP during the first seconds of the subsequent HUT (-17.9 +/- 1.4 mmHg) compared with HUT alone (-12.4 +/- 1.2 mmHg, P <0.05) despite a greater rise in stroke volume (Doppler ultrasound) and cardiac output over this brief time period in the HDT-HUT trials compared with the HUT trials (thereafter stroke volume fell under both conditions). The greater fall in ELAP was associated with an exaggerated increase in leg blood flow (femoral artery Doppler ultrasound) and was therefore largely (70%) attributable to an exaggerated rise in estimated leg vascular conductance, confirming our hypotheses. Thus brief exposure to -G(z) stress leads to an exaggerated fall in ELAP during subsequent HUT, owing to an exaggerated increase in estimated leg vascular conductance.

Diversion of blood flow from noncompliant to compliant vasculature in awake dogs: mechanical impact on right atrial pressure.

The distribution of cardiac output between compliant vasculature (e.g., splanchnic organs and skin) and noncompliant vasculature (e.g., skeletal muscle) is proposed to constitute an important determinant of the amount of blood available to the heart (central blood volume and pressure). The aim here was to directly test the hypothesis that diversion of blood flow from a relatively noncompliant vasculature (muscle) to compliant vasculature (splanchnic organs and skin) acts to reduce right atrial pressure. The approach was to inflate an occluder cuff on the terminal aorta for 30 s in one of two modes of ventricular pacing in five awake dogs with atrioventricular block and autonomic blockade. In one trial, cardiac output was maintained constant, meaning cuff inflation caused a portion of terminal aortic flow (a noncompliant circulation) to be diverted to the splanchnic and skin circulations (compliant circulations). In the other trial, arterial pressure was maintained constant, meaning blood flow to these other regions did not change. The response of right atrial pressure (corrected for differences in arterial pressure between the two trials) fit our hypothesis, being lower when blood flow was diverted to compliant regions. We conclude that a small (4% of cardiac output) diversion of blood flow from a noncompliant region to a compliant region reduces right atrial pressure by 0.7 mmHg.

Is there a threshold duration of vascular occlusion for hindlimb reactive hyperemia?

Relatively brief changes in perfusion pressure and flow through arterioles occur in a number of conditions, such as in the flying environment and during such common everyday activities such as bending forward at the waist. Also, brief periods of negative vertical acceleration (G(z)) stress, which reduces perfusion in the lower body, has been shown to impair the regulation of arterial pressure during subsequent positive G(z) stress. To examine the contribution that reactive hyperemia makes in these settings, studies on the hindlimb circulation of anesthetized rats (n = 8) were carried out by imposing graded duration vascular occlusion (1, 2, 4, 10, and 30 s) to test the hypothesis that there is a threshold duration of reduction in perfusion that must be exceeded for reactive hyperemia to be triggered. Vascular conductance responses to 1 s of terminal aortic occlusion were no different before and after myogenic responses were blocked with nifedipine, indicating that 1 s of occlusion failed to elicit reactive hyperemia. Two seconds of occlusion elicited a small but significant elevation in hindlimb vascular conductance. The magnitude of the reactive hyperemia was graded in direct relation to the duration of occlusion for the 2-, 4-, and 10-s periods of occlusion and appeared to be approaching a plateau for the 30-s occlusion. Thus there is a threshold duration of terminal aortic occlusion (approximately 2 s) required to elicit reactive hyperemia in the hindlimbs of anesthetized rats, and the reactive hyperemia that results possesses a threat to the regulation of arterial pressure.

Immediate exercise hyperemia: contributions of the muscle pump vs. rapid vasodilation.

A striking characteristic of the blood flow adaptation at exercise onset is the immediate and substantial increase in the first few (0-5 s) seconds of exercise. The purpose of this mini-review is to put into context the present evidence regarding mechanisms responsible for this phase of exercise hyperemia. One potential mechanism that has received much attention is the mechanical effect of muscle contraction (the muscle pump). The rapid vasodilatory mechanism(s) is another possible mechanism that has recently been shown to exist. This review will provide the reader with 1) an understanding of the basic physics of blood flow and the theories of muscle pump function, 2) a critical examination of evidence both for and against the contribution of the muscle pump or rapid vasodilatory mechanisms, and 3) an awareness of the limitations and impact of experimental models and exercise modes on the contribution of each of these mechanisms to the immediate exercise hyperemia. The inability to measure microvenular pressure continues to limit investigators to indirect assessments of the muscle pump vs. vasodilatory mechanism contributions to immediate exercise hyperemia in vivo. Future research directions should include examination of muscle-contraction-induced resistance vessel distortion as a trigger for rapid smooth muscle relaxation and further investigation into the exercise mode dependency of muscle pump vs. rapid vasodilatory contributions to immediate exercise hyperemia.

Role of estrogen in nitric oxide- and prostaglandin-dependent modulation of vascular conductance during treadmill locomotion in rats.

Endothelial production of nitric oxide (NO) and prostaglandins (PG) may be greater in females than in males, increasing vasodilatory responses in females. Does sex influence the cardiovascular responses to dynamic exercise through estrogen-dependent modulation of NO and PG vasodilatory pathways? After the administration of hexamethonium, we assessed terminal aortic blood flow (TAQ), mean arterial pressure (MAP), and hindlimb vascular conductance (VC) in four groups of rats (6 males, 5 females, 5 ovariectomized females, and 6 ovariectomized females with chronic estrogen supplementation) during graded mild-intensity treadmill locomotion (5-15 m/min, 0 degrees grade, 2 min). All rats repeated exercise after cyclooxygenase inhibition (indomethacin) and then again after NO synthase inhibition (nitro-l-arginine methyl ester) to examine the roles of NO and PG. Regression analysis was used to determine the influence of sex and plasma 17beta-estradiol on TAQ, MAP, and VC. The analysis revealed that female sex did not influence TAQ but reduced MAP and increased VC at rest and during exercise conditions. Plasma 17beta-estradiol (measured by immunoassay) significantly decreased MAP and increased TAQ and VC, irrespective of sex. Cyclooxygenase inhibition eliminated the significant association between MAP and estrogen, suggesting that estrogenic modulation occurred through PG-dependent processes. In contrast, the significant influence of estrogen on TAQ and VC was eliminated after NO synthase inhibition. On the basis of the overall findings of this study, estrogen influenced the vascular responses to dynamic exercise through PG- and NO-dependent pathways, but this occurred independent of sex.

Epidermal cells accelerate the restoration of the blood flow in diabetic ischemic limbs.

Epidermal progenitor cells (EpPCs) were long thought to be unipotent, giving rise only to other keratinocytes but recent studies question this assumption. Here, we investigated whether mouse EpPCs can adopt other antigenic and functional phenotypes. To test this, we injected freshly isolated and cultured EpPCs and transient amplifying cells into diabetic and non-diabetic mouse ischemic hindlimb and followed the cells' fate and the recovery of the ischemic limb blood flow over time. Both freshly isolated and cultured EpPCs and transient amplifying cells were incorporated into the vasculature of the ischemic limb 2 and 5 weeks post-injection, and some expressed endothelial cell but not keratinocyte antigens. Additionally, in the non-diabetic animals, first transient amplifying cells and then EpPCs accelerated the restoration of the blood flow. By contrast, in diabetic animals, only injected EpPCs or unsorted epidermal cells accelerated the restoration of the blood flow. These data indicate that epidermal cells can adopt non-skin phenotypes and functions, and that this apparent pluripotency is not lost by differentiation of EpPCs into transient amplifying cells. They also suggest that epidermal cell therapy might be of therapeutic value in the treatment of diabetic ischemia. Finally, because epidermal cells are readily accessible and expandable, they appear to be ideally suited for use as a non-viral gene delivery therapy.

Passive regulation of cardiac output during exercise by the elastic characteristics of the peripheral circulation.

A change in cardiac output induced by a change in cardiac performance is accompanied by opposite changes in cardiac filling pressure owing to the resistive and capacitive properties of blood vessels. The inverse relationship between cardiac output and cardiac filling pressure provides a passive (hydraulic) regulatory mechanism that functions to keep cardiac output constant during rest and exercise.

Augmentation of the push-pull effect by terminal aortic occlusion during head-down tilt.

Tolerance to positive vertical acceleration (Gz) gravitational stress is reduced when positive Gz stress is preceded by exposure to hypogravity, which is called the "push-pull effect." The purpose of this study was to test the hypothesis that baroreceptor reflexes contribute to the push-pull effect by augmenting the magnitude of simulated hypogravity and thereby augmenting the stimulus to the baroreceptors. We used eye-level blood pressure as a measure of the effectiveness of the blood pressure regulatory systems. The approach was to augment the magnitude of the carotid hypertension (and the hindbody hypotension) when hypogravity was simulated by head-down tilt by mechanically occluding the terminal aorta and the inferior vena cava. Sixteen anesthetized Sprague-Dawley rats were instrumented with a carotid artery catheter and a pneumatic vascular occluder cuff surrounding the terminal aorta and inferior vena cava. Animals were restrained and subjected to a control gravitational (G) profile that consisted of rotation from 0 Gz to 90 degrees head-up tilt (+1 Gz) for 10 s and a push-pull G profile consisting of rotation from 0 Gz to 90 degrees head-down tilt (-1 Gz) for 2 s immediately preceding 10 s of +1 Gz stress. An augmented push-pull G profile consisted of terminal aortic vascular occlusion during 2 s of head-down tilt followed by 10 s of +1 Gz stress. After the onset of head-up tilt, the magnitude of the fall in eye-level blood pressure from baseline was -20 +/- 1.3, -23 +/- 0.7, and -28 +/- 1.6 mmHg for the control, push-pull, and augmented push-pull conditions, respectively, with all three pairwise comparisons achieving statistically significant differences (P < 0.01). Thus augmentation of negative Gz stress with vascular occlusion increased the magnitude of the push-pull effect in anesthetized rats subjected to tilting.

Hypotensive effect of push-pull gravitational stress occurs after autonomic blockade.

The "push-pull" effect denotes the reduced tolerance to +Gz (hypergravity) when +Gz stress is preceded by exposure to hypogravity, i.e., fractional, zero, or negative Gz. Previous studies have implicated autonomic reflexes as a mechanism contributing to the push-pull effect. The purpose of this study was to test the hypothesis that nonautonomic mechanisms can cause a push-pull effect, by using eye-level blood pressure as a measure of G tolerance. The approach was to impose control (30 s of 30 degrees head-up tilt) and push-pull (30 s of 30 degrees head-up tilt immediately preceded by 10 s of -15 degrees headdown tilt) gravitational stress after administration of hexamethonium (10 mg/kg) to inhibit autonomic ganglionic neurotransmission in four dogs. The animals were chronically instrumented with arterial and venous catheters, an ascending aortic blood flow transducer, ventricular pacing electrodes, and atrioventicular block. The animals were paced at 75 beats/min throughout the experiment. The animals were sedated with acepromazine and lightly restrained in lateral recumbency on a tilt table. After the onset of head-up tilt, the magnitude of the fall in eye-level blood pressure from baseline was -27.6 +/- 2.3 and -37.9 +/- 2.7 mmHg for the control and push-pull trials, respectively (P < 0.05). Cardiac output fell similarly in both conditions. Thus a push-pull effect attributable to a rise in total vascular conductance occurs when autonomic function is inhibited.

Muscle pump function during locomotion: mechanical coupling of stride frequency and muscle blood flow.

We imposed opposing oscillations in treadmill speed and grade on nine rats to test for direct mechanical coupling between stride frequency and hindlimb blood flow. Resting hindlimb blood flow was 15.5 +/- 1.7 ml/min. For 90 s at 7.5 m/min, rats alternated walking at -10 degrees for 10 s and +10 degrees for 10 s. This elicited oscillations in hindlimb blood flow having an amplitude of 4.1 +/- 0.5 ml/min (18% of mean flow) with a delay presumably due to metabolic vasodilation. Similar oscillations in speed (5.5-9.5 m/min) elicited oscillations in hindlimb blood flow (amplitude 3.4 +/- 0.5 ml/min, 15% of mean flow) with less of a delay, possibly due to changes in vasodilation and muscle pump function. We then simultaneously imposed these speed and grade oscillations out of phase (slow uphill, fast downhill). The rationale was that the oscillations in vasodilation evoked by the opposing oscillations in speed and grade would cancel each other, thereby testing the degree to which stride frequency affects hindlimb blood flow directly (i.e., muscle pumping). Opposing oscillations in speed and grade evoked oscillations in hindlimb blood flow having an amplitude of 3.3 +/- 0.6 ml/min (16% of mean flow) with no delay and directly in phase with the changes in speed and stride frequency. The finding that hindlimb blood flow changes directly with speed (when vasodilation caused by changes in speed and grade oppose each other) indicates that there is a direct coupling of stride frequency and hindlimb blood flow (i.e., muscle pumping).

Delay of muscle vasodilation to changes in work rate (treadmill grade) during locomotion.

Previous studies examining the delay to the onset of vasodilation have primarily focused on the onset of exercise, a setting complicated by the fact that the muscle pump and the vasodilator systems are both activated, making it difficult to attribute changes in blood flow to one or both. The goal here was to determine the delay to the onset of vasodilation after changes in work rate imposed by changes in treadmill grade (work intensity) during locomotion at a steady speed. The rationale was that constant speed would help ensure constant muscle pump activity (contraction frequency) such that vasodilator responses could be examined in isolation. Seven Sprague-Dawley rats underwent three trials each in which treadmill incline was suddenly ( approximately 1 s) elevated from -10 degrees to +10 degrees. The delay to the onset of vasodilation averaged 5.0 +/- 1.8 s, and this delay was not altered by inhibition of nitric oxide synthase. Similar or longer delays were seen during sinusoidal exercise. Thus there is a significant delay before the onset of vasodilation after an increase in work intensity (muscle force) during locomotory exercise at constant speed.

Role of the autonomic nervous system in push-pull gravitational stress in anesthetized rats.

Tolerance to +G(z) stress is reduced by preceding exposure to -G(z) (push-pull effect). The mechanism(s) responsible for this effect are not fully understood, although the arterial baroreceptor reflexes have been implicated. We investigated the integrative response of the autonomic nervous system by studying responses to gravitational stress before and after autonomic function was inhibited by hexamethonium in 10 isoflurane-anesthetized male and female Sprague-Dawley rats. Animals were restrained supine and subjected to two rotations imposed about the x-axis: 1) a control G profile consisting of rotation from 0 G(z) (+1 G(y)) to 90 degrees head-up tilt (+1 G(z)) for 10 s and 2) a push-pull G profile consisting of rotation from 0 G(z) to 90 degrees head-down tilt (-1 G(z)) for 2 s immediately preceding 10 s of +1 G(z) stress. Eight G profiles consisting of equal numbers of control and push-pull trials were imposed by using a counterbalanced design. We found that hexamethonium lowered baseline arterial pressure and abolished the push-pull effect. The lack of a push-pull effect after autonomic blockade persisted when arterial pressure was restored to baseline levels by phenylephrine infusion. Lowering baseline arterial pressure by sodium nitroprusside infusion or by hemorrhage when autonomic function was intact also abolished the push-pull effect. We conclude that intact autonomic function and a normal baseline arterial pressure are needed for expression of the push-pull effect in anesthetized rats subjected to tilting.