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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
NASA NTRS1992

Pulmonary hypoxic vasoconstriction: how strong? How fast?

We have developed a minimally invasive technique for studying regional blood flow in conscious sheep, bypassing the complications of open-chest surgery, flow probes and tracer infusion. We quantitate regional perfusion continuously on the basis of regional clearance of methane (methane is produced in the sheep rumen, enters the circulation and is eliminated nearly completely (greater than 95%) in the lung). Tracheal intubation with a dual-lumen catheter isolates the gas exchange of the right apical lobe (RAL; less than 15% of the lung) from that of the remainder of the lung, which serves as a control (CL). We measure RAL and CL methane elimination by entraining expirates in constant flows, sampled continuously for methane. Results obtained with this technique and from regional oxygen uptake are in excellent agreement. We have found that hypoxic vasoconstriction is far more potent and stable during eucapnic hypoxia than during hypocapnic hypoxia. The time course of the vasoconstriction suggests that many of the data in the literature may have been obtained prior to steady state.

NASA Discipline Regulatory Physiology↗
NASA NTRS1998

Effects of posture on blood flow diversion by hypoxic pulmonary vasoconstriction in dogs

We used differential excretion of sulphur hexafluoride from the left and right lung to measure blood flow diversion by hypoxic pulmonary vasoconstriction (HPV) in the prone and supine positions in dogs (n = 9). Gas exchange was assessed using the multiple inert gas elimination technique. Blood flow diversion from the hypoxic (3% oxygen) left lung was mean 70.7 (SD 11.2)% in the supine compared with 57.0 (12.1)% in the prone position (P < 0.02). The supine position was associated with increased perfusion to low VA/Q regions (P < 0.05). The increased flow diversion with hypoxia in the supine position was associated with more ventilation to high VA/Q regions (P < 0.05). We conclude that flow diversion by hypoxic pulmonary vasoconstriction is greater in the supine position. This effect could contribute to the variable response in gas exchange with positioning in patients with ARDS.

Non-NASA Center↗
NASA NTRS1971

Splanchnic vasoconstriction in hyperthermic man - Role of falling blood pressure.

Results of a study in which six supine resting subjects, wearing water-perfused suits, had body skin temperature controlled at 35 C for 30 min (control period), then rapidly increased to 40.5 C for 43 to 50 min (heating period) in a two-part experiment. In the first part of the experiment arterial mean pressure (MP) in three men was increased back to, or above control levels at the 30 to 35th min of heating by total occlusion of both legs for 8 to 10 min. Splanchnic blood flow (SBF), which had fallen from 1.4 to 0.9 L/min at occlusion, rose only 0.05 L/min during occlusion. Splanchnic vascular resistance (SVR) rose throughout heating and occlusion. In the second part of the experiment (three men) SBF fell despite a spontaneous rise in MP and aortic pulse pressure prior to leg occlusion. Cardiac output (CO) was measured just before, during and after occlusion. Occlusion raised MP 10 to 15 mm Hg and reduced CO only slightly. It is concluded that falling MP or aortic pulse pressure are not major causes of the splanchnic vasoconstriction in response to heating man.

Rowell, L. B.↗
NASA NTRS2002

Obstructive apnea during sleep is associated with peripheral vasoconstriction

Obstructive apnea during sleep is associated with a substantial transient blood pressure elevation. The mechanism of this pressor response is unclear. In this study we measured muscle sympathetic nerve activity (MSNA), mean arterial pressure (Psa), and mean limb blood velocity as an index of blood flow (MBV, Doppler) and calculated changes in limb vascular resistance during and after apneas during both wakefulness and sleep in patients with the obstructive sleep apnea syndrome. Immediately postapnea during sleep Psa increased significantly compared with the earlier stages of apnea and this was preceded by a rise of MSNA (n = 5). In contrast to blood pressure, MBV remained unchanged. Because resistance = blood pressure/blood flow, limb vascular resistance increased by 29 +/- 8% from late apnea to postapnea (n = 7, p < 0.002). Voluntary breathhold maneuvers during room air exposure evoked similar responses (n = 10). Supplemental oxygen administered via nonrebreather face mask attenuated the MSNA and vasoconstrictor responses to obstructive (n = 2) and voluntary apneas (n = 10). Our data suggest that obstructive apneas in patients with the obstructive apnea syndrome are accompanied by transient limb vasoconstriction. This vasoconstrictor response appears to be, at least in part, mediated by the sympathetic nervous system and may be linked to hypoxia.

NASA Discipline Cardiopulmonary↗
NASA NTRS2003

Effects of repeated Valsalva maneuver straining on cardiac and vasoconstrictive baroreflex responses

INTRODUCTION: We hypothesized that repeated respiratory straining maneuvers (repeated SM) designed to elevate arterial BPs (arterial baroreceptor loading) would acutely increase baroreflex responses. METHODS: We tested this hypothesis by measuring cardiac baroreflex responses to carotid baroreceptor stimulation (neck pressures), and changes in heart rate and diastolic BP after reductions in BP induced by a 15-s Valsalva maneuver in 10 female and 10 male subjects at 1, 3, 6, and 24 h after performing repeated SM. Baroreflex responses were also measured in each subject at 1, 3, 6, and 24 h at the same time on a separate day without repeated SM (control) in a randomized, counter-balanced cross-over experimental design. RESULTS: There was no statistical difference in carotid-cardiac and peripheral vascular baroreflex responses measured across time following repeated SM compared with the control condition. Integrated cardiac baroreflex response (deltaHR/ deltaSBP) measured during performance of a Valsalva maneuver was increased by approximately 50% to 1.1 +/- 0.2 bpm x mm Hg(-1) at 1 h and 1.0 +/- 0.1 bpm x mm Hg(-1) at 3 h following repeated SM compared with the control condition (0.7 +/- 0.1 bpm x mm Hg(-1) at both 1 and 3 h, respectively). However, integrated cardiac baroreflex response after repeated SM returned to control levels at 6 and 24 h after training. These responses did not differ between men and women. CONCLUSIONS: Our results are consistent with the notion that arterial baroreceptor loading induced by repeated SM increased aortic, but not carotid, cardiac baroreflex responses for as long as 3 h after repeated SM. We conclude that repeated SM increases cardiac baroreflex responsiveness which may provide patients, astronauts, and high-performance aircraft pilots with protection from development of orthostatic hypotension.

NASA Discipline Cardiopulmonary↗
NASA NTRS2000

Cerebral vasoconstriction precedes orthostatic intolerance after parabolic flight

The effects of brief but repeated bouts of micro- and hypergravity on cerebrovascular responses to head-up tilt (HUT) were examined in 13 individuals after (compared to before) parabolic flight. Middle cerebral artery mean flow velocity (MCA MFV; transcranial Doppler ultrasound), eye level blood pressure (BP) and end tidal CO(2) (P(ET)CO(2)) were measured while supine and during 80 degrees HUT for 30 min or until presyncope. In the postflight tests subjects were classified as being orthostatically tolerant (OT) (n = 7) or intolerant (OI) (n = 6). BP was diminished with HUT in the OT group in both tests (p < 0.05) whereas postflight BP was not different from supine in the OI group. Postflight compared to preflight, the reduction in P(ET)CO(2) with HUT (p < 0.05) increased in both groups, although significantly so only in the OI group (p < 0.05). The OI group also had a significant decrease in supine MCA MFV postflight (p < 0.05) that was unaccompanied by a change in supine P(ET)CO(2). The decrease in MCA MFV that occurred during HUT in both groups preflight (p < 0.05) was accentuated only in the OI group postflight, particularly during the final 30 s of HUT (p < 0.05). However, this accentuated decrease in MCA MFV was not correlated to the greater decrease in P(ET)CO(2) during the same period (R = 0.20, p = 0.42). Although cerebral vascular resistance (CVR) also increased in the OI group during the last 30 s of HUT postflight (p < 0.05), the dynamic autoregulatory gain was not simultaneously changed. Therefore, we conclude that in the OI individuals, parabolic flight was associated with cerebral hypoperfusion following a paradoxical augmentation of CVR by a mechanism that was not related to changes in autoregulation nor strictly to changes in P(ET)CO(2).

Parabolic Flight↗
NASA NTRS1999

Age, splanchnic vasoconstriction, and heat stress during tilting

During upright tilting, blood is translocated to the dependent veins of the legs and compensatory circulatory adjustments are necessary to maintain arterial pressure. For examination of the effect of age on these responses, seven young (23 +/- 1 yr) and seven older (70 +/- 3 yr) men were head-up tilted to 60 degrees in a thermoneutral condition and during passive heating with water-perfused suits. Measurements included heart rate (HR), cardiac output (Qc; acetylene rebreathing technique), central venous pressure (CVP), blood pressures, forearm blood flow (venous occlusion plethysmography), splanchnic and renal blood flows (indocyanine green and p-aminohippurate clearance), and esophageal and mean skin temperatures. In response to tilting in the thermoneutral condition, CVP and stroke volume decreased to a greater extent in the young men, but HR increased more, such that the fall in Qc was similar between the two groups in the upright posture. The rise in splanchnic vascular resistance (SVR) was greater in the older men, but the young men increased forearm vascular resistance (FVR) to a greater extent than the older men. The fall in Qc during combined heat stress and tilting was greater in the young compared with older men. Only four of the young men versus six of the older men were able to finish the second tilt without becoming presyncopal. In summary, the older men relied on a greater increase in SVR to compensate for a reduced ability to constrict the skin and muscle circulations (as determined by changes in FVR) during head-up tilting.

NASA Discipline Cardiopulmonary↗
NASA NTRS1998

Raised cerebrovascular resistance in idiopathic orthostatic intolerance: evidence for sympathetic vasoconstriction

Patients with idiopathic orthostatic intolerance (IOI) exhibit symptoms suggestive of cerebral hypoperfusion and an excessive decrease in cerebral blood flow associated with standing despite sustained systemic blood pressure. In 9 patients (8 women and 1 man aged 22 to 48 years) with IOI, we tested the hypothesis that volume loading (2000 cc normal saline) and alpha-adrenoreceptor agonism improve systemic hemodynamics and cerebral perfusion and that the decrease in cerebral blood flow with head-up tilt (HUT) could be attenuated by alpha-adrenoreceptor blockade with phentolamine. At 5 minutes of HUT, volume loading (-20+/-3.2 bpm) and phenylephrine (-18+/-3.4 bpm) significantly reduced upright heart rate compared with placebo; the effect was diminished at the end of HUT. Phentolamine substantially increased upright heart rate at 5 minutes (20+/-3.7 bpm) and at the end of HUT (14+/-5 bpm). With placebo, mean cerebral blood flow velocity decreased by 33+/-6% at the end of HUT. This decrease in cerebral blood flow with HUT was attenuated by all 3 interventions. We conclude that in patients with IOI, HUT causes a substantial decrease in cerebrovascular blood flow velocity. The decrease in blood flow velocity with HUT can be attenuated with interventions that improve systemic hemodynamics and therefore decrease reflex sympathetic activation. Moreover, alpha-adrenoreceptor blockade also blunts the decrease in cerebral blood flow with HUT but at the price of deteriorated systemic hemodynamics. These observations may suggest that in patients with IOI, excessive sympathetic activity contributes to the paradoxical decrease in cerebral blood flow with upright posture.

Non-NASA Center↗
NASA NTRS1994

Cerebral versus systemic hemodynamics during graded orthostatic stress in humans

BACKGROUND: Orthostatic syncope is usually attributed to cerebral hypoperfusion secondary to systemic hemodynamic collapse. Recent research in patients with neurocardiogenic syncope has suggested that cerebral vasoconstriction may occur during orthostatic hypotension, compromising cerebral autoregulation and possibly contributing to the loss of consciousness. However, the regulation of cerebral blood flow (CBF) in such patients may be quite different from that of healthy individuals, particularly when assessed during the rapidly changing hemodynamic conditions associated with neurocardiogenic syncope. To be able to interpret the pathophysiological significance of these observations, a clear understanding of the normal responses of the cerebral circulation to orthostatic stress must be obtained, particularly in the context of the known changes in systemic and regional distributions of blood flow and vascular resistance during orthostasis. Therefore, the specific aim of this study was to examine the changes that occur in the cerebral circulation during graded reductions in central blood volume in the absence of systemic hypotension in healthy humans. We hypothesized that cerebral vasoconstriction would occur and CBF would decrease due to activation of the sympathetic nervous system. We further hypothesized, however, that the magnitude of this change would be small compared with changes in systemic or skeletal muscle vascular resistance in healthy subjects with intact autoregulation and would be unlikely to cause syncope without concomitant hypotension. METHODS AND RESULTS: To test this hypothesis, we studied 13 healthy men (age, 27 +/- 7 years) during progressive lower body negative pressure (LBNP). We measured systemic flow (Qc is cardiac output; C2H2 rebreathing), regional forearm flow (FBF; venous occlusion plethysmography), and blood pressure (BP; Finapres) and calculated systemic (SVR) and forearm (FVR) vascular resistances. Changes in brain blood flow were estimated from changes in the blood flow velocity in the middle cerebral artery (VMCA) using transcranial Doppler. Pulsatility (systolic minus diastolic/mean velocity) normalized for systemic arterial pressure pulsatility was used as an index of distal cerebral vascular resistance. End-tidal PACO2 was closely monitored during LBNP. From rest to maximal LBNP before the onset of symptoms or systemic hypotension, Qc and FBF decreased by 29.9% and 34.4%, respectively. VMCA decreased less, by 15.5% consistent with a smaller decrease in CBF. Similarly, SVR and FVR increased by 62.8% and 69.8%, respectively, whereas pulsatility increased by 17.2%, suggestive of a mild degree of small-vessel cerebral vasoconstriction. Seven of 13 subjects had presyncope during LBNP, all associated with a sudden drop in BP (29 +/- 9%). By comparison, hyperventilation alone caused greater changes in VMCA (42 +/- 2%) and pulsatility but never caused presyncope. In a separate group of 3 subjects, superimposition of hyperventilation during highlevel LBNP caused a further decrease in VMCA (31 +/- 7%) but no change in BP or level of consciousness. CONCLUSIONS: We conclude that cerebral vasoconstriction occurs in healthy humans during graded reductions in central blood volume caused by LBNP. However, the magnitude of this response is small compared with changes in SVR or FVR during LBNP or other stimuli known to induce cerebral vasoconstriction (hypocapnia). We speculate that this degree of cerebral vasoconstriction is not by itself sufficient to cause syncope during orthostatic stress. However, it may exacerbate the decrease in CBF associated with hypotension if hemodynamic instability develops.

NASA Discipline Cardiopulmonary↗
NASA NTRS1999

Cardiovascular Session Summary

It was apparent that the bed-rest and spaceflight data indicated that decreases in plasma volume and cardiac atrophy along with cardiac remodeling were fundamental changes which predisposed many astronauts to post flight orthostatic intolerance. Despite the recently acquired in-flight and post-flight muscle sympathetic nerve activity findings suggesting that the sympathetic nerve responses were appropriate there remains significant contrary data from bed-rest studies, post- flight stand tests and hind-limb unweighted rat studies that suggest that the vasoconstrictive responses were compromised at least insufficient in susceptible individuals. The key issues raised is whether a diminished increase in sympathetic activity from baseline without changes in 254 First Biennial Space Biomedical Investigators'Workshop Cardiovascular peak response or receptor adaptations is an abnormal response or is an individual variance of response to the accentuated decrease in stroke volume. Data relating autonomic neural control of heart rate were presented to suggest that the vagal and sympathetic control of heart rate was attenuated. Also, bed-rest and space flight induced attenuated baroreflex control of heart rate was shown to be restored to pre-bedrest function by one bout of maximal dynamic exercise. However, these data were confounded by relying on the use of R-R interval as a measure of efferent responses of the baroreflex during a condition in which the baseline heart rate was changed. Clearly the idea that the autonomic control of heart rate may be changed by microgravity needs further investigation. This direction is suggested despite the fact that in the triple product (HR x SV x TPR = MAP) assessment of the regulation of arterial blood pressure during orthostasis the role of the HR reflex may be less influential than that associated. with cardiac atrophy (SV changes) and aberrant sympathetic vasoconstriction (resistance) changes. Although sympathetic nerve activity responses in-flight and post-flight on neurolab appeared appropriate, enough bed-rest and post-flight stand test data, along with animal model data suggest that vasoconstriction was compromised. The mechanism of this compromised vasoconstriction needs to be delineated. Other major findings concerning microgravity and physiological regulatory systems are that: I . Thermoregulatory adaptation appear to suggest some decrements in the control of cutaneous vasodilation and sweating; 2. Calcium resorption and dietary calcium need to be defined for differing durations of spaceflight, especially as the effects of excess calcium on vasomotor function appears to be detrimental; 3. Neurohumoral mechanisms of microgravity induced changes in neural function and the regulation of plasma volume and total body water, bone resorption and autonomic neural control of the circulation need further delineation; 4. As performance of work tasks become prolonged, the mechanisms of blood pressure regulation in microgravity needs to be used in the recovery period from prolonged work tasks.

Raven, Peter↗
NASA NTRS2003

Renal vascular responses to static handgrip: role of muscle mechanoreflex

During exercise, the sympathetic nervous system is activated, which causes vasoconstriction. The autonomic mechanisms responsible for this vasoconstriction vary based on the particular tissue being studied. Attempts to examine reflex control of the human renal circulation have been difficult because of technical limitations. In this report, the Doppler technique was used to examine renal flow velocity during four muscle contraction paradigms in conscious humans. Flow velocity was divided by mean arterial blood pressure to yield an index of renal vascular resistance (RVR). Fatiguing static handgrip (40% of maximal voluntary contraction) increased RVR by 76%. During posthandgrip circulatory arrest, RVR remained above baseline (2.1 +/- 0.2 vs. 2.8 +/- 0.2 arbitrary units; P < 0.017) but was only 40% of the end-grip RVR value. Voluntary biceps contraction increased RVR within 10 s of initiation of contraction. This effect was not associated with an increase in blood pressure. Finally, involuntary biceps contraction also raised RVR. We conclude that muscle contraction evokes renal vasoconstriction in conscious humans. The characteristic of this response is consistent with a primary role for mechanically sensitive afferents. This statement is based on the small posthandgrip circulatory arrest response and the vasoconstriction that was observed with involuntary biceps contraction.

NASA Discipline Neuroscience↗
NASA NTRS2003

Effects of 14 days of head-down tilt bed rest on cutaneous vasoconstrictor responses in humans

This study tested the hypothesis that head-down tilt bed rest (HDBR) reduces adrenergic and nonadrenergic cutaneous vasoconstrictor responsiveness. Additionally, an exercise countermeasure group was included to identify whether exercise during bed rest might counteract any vasoconstrictor deficits that arose during HDBR. Twenty-two subjects underwent 14 days of strict 6 degrees HDBR. Eight of these 22 subjects did not exercise during HDBR, while 14 of these subjects exercised on a supine cycle ergometer for 90 min a day at 75% of pre-bed rest heart rate maximum. To assess alpha-adrenergic vasoconstrictor responsiveness, intradermal microdialysis was used to locally administer norepinephrine (NE), while forearm skin blood flow (SkBF; laser-Doppler flowmetry) was monitored over microdialysis membranes. Nonlinear regression modeling was used to identify the effective drug concentration that caused 50% of the cutaneous vasoconstrictor response (EC(50)) and minimum values from the SkBF-NE dose-response curves. In addition, the effects of HDBR on nonadrenergic cutaneous vasoconstriction were assessed via the venoarteriolar response of the forearm and leg. HDBR did not alter EC(50) or the magnitude of cutaneous vasoconstriction to exogenous NE administration regardless of whether the subjects exercised during HDBR. Moreover, HDBR did not alter the forearm venoarteriolar response in either the control or exercise groups during HDBR. However, HDBR significantly reduced the magnitude of cutaneous vasoconstriction due to the venoarteriolar response in the leg, and this response was similarly reduced in the exercise group. These data suggest that HDBR does not alter cutaneous vasoconstrictor responses to exogenous NE administration, whereas cutaneous vasoconstriction of the leg due to the venoarteriolar response is reduced after HDBR. It remains unclear whether attenuated venoarteriolar responses in the lower limbs contribute to reduced orthostatic tolerance after bed rest and spaceflight.

NASA Discipline Cardiopulmonary↗
NASA NTRS1974

Cardiovascular response to apneic immersion in cool and warm water

The influence of prior exposure to cool water and the influence of lung volume on the responses to breath holding were examined. The bradycardia and vasoconstriction that occur during breath-hold diving in man are apparently the resultant of stimuli from apnea, relative expansion of the thorax, lung volume, esophageal pressure, face immersion, and thermal receptor stimulation. It is concluded that the bradycardia and vasoconstriction associated with breath holding during body immersion are not attenuated by a preexisting bradycardia and vasoconstriction due to cold.

Folinsbee, L.↗
NASA NTRS2002

Effect of whole-body and local heating on cutaneous vasoconstrictor responses in humans

Animal studies suggest that alpha-adrenergic-mediated vasoconstriction is compromised during whole-body heating. The purpose of this study was to identify whether whole-body heating and/or local surface heating reduce cutaneous alpha-adrenergic vasoconstrictor responsiveness in human skin. Protocol I: Six subjects were exposed to neutral skin temperature (i.e., 34 degrees C), whole-body heating, and local heating of forearm skin to increase skin blood flow to the same relative magnitude as that observed during whole-body heating. Protocol II: In eight subjects forearm skin was locally heated to 34, 37, 40, and 42 degrees C. During both protocols, alpha-adrenergic vasoconstrictor responsiveness was assessed by local delivery of norepinephrine (NE) via intradermal microdialysis. Skin blood flow was continuously monitored over each microdialysis membrane via laser-Doppler flowmetry. In protocol I, whole-body and local heating caused similar increases in cutaneous vascular conductance (CVC). The EC50 (log NE dose) of the dose-response curves for both whole body (-4.2 +/- 0.1 M) and local heating (-4.7 +/- 0.4 M) were significantly greater (i.e., high dose required to cause 50% reduction in CVC) relative to neutral skin temperature (- 5.6 +/- 0.0 M; P<0.05 for both). In both local and whole-body heated conditions CVC did not return to pre-heating values even at the highest dose of NE. In protocol II, calculated EC50 for 34, 37, 40, and 42 degrees C local heating was - 5.5 +/- 0.4, -4.6 +/- 0.3, -4.5 +/- 0.3, - 4.2 +/- 0.4 M, respectively. Statistical analyses revealed that the EC50 for 37,40 and 42 degrees C were significantly greater than the EC50 for 34 degrees C. These results indicate that even during administration of high concentrations of NE, alpha-adrenergic vasoconstriction does not fully compensate for local heating and whole-body heating induced vasodilatation in young, healthy subjects. Moreover, these data suggest that elevated local temperatures, above 37 degrees C, and whole-body heating similarly attenuate cutaneous alpha-adrenergic vasoconstriction responsiveness.

Non-NASA Center↗
NASA NTRS2002

Limb neurovascular control during altered otolithic input in humans

Head-down rotation (HDR), which activates the vestibulosympathetic reflex, increases leg muscle sympathetic nerve activity (MSNA) and produces calf vasoconstriction with no change in either cardiac output or arterial blood pressure. Based on animal studies, it was hypothesized that differential control of arm and leg MSNA explains why HDR does not alter arterial blood pressure. Fifteen healthy subjects were studied. Heart rate, arterial blood pressure, forearm and calf blood flow, and leg MSNA responses were measured during HDR in these subjects. Simultaneous recordings of arm and leg MSNA were obtained from five of the subjects. Forearm and calf blood flow, vascular conductances, and vascular resistances were similar before HDR, as were arm and leg MSNA. HDR elicited similar significant increases in leg (Delta 6 +/- 1 bursts min(-1); 59 +/- 16 % from baseline) and arm MSNA (Delta 5 +/- 1 bursts min(-1); 80 +/- 28 % from baseline). HDR significantly decreased calf (-19 +/- 2 %) and forearm vascular conductance (-12 +/- 2 %) and significantly increased calf (25 +/- 4 %) and forearm vascular resistance (15 +/- 2 %), with ~60 % greater vasoconstriction in the calf than in the forearm. Arterial blood pressure and heart rate were not altered by HDR. These results indicate that there is no differential control of MSNA in the arm and leg during altered feedback from the otolith organs in humans, but that greater vasoconstriction occurs in the calf than in the forearm. These findings indicate that vasodilatation occurs in other vascular bed(s) to account for the lack of increase in arterial blood pressure during HDR.

Non-NASA Center↗
NASA NTRS2000

Endogenous circulating sympatholytic factor in orthostatic intolerance

Sympathotonic orthostatic hypotension (SOH) is an idiopathic syndrome characterized by tachycardia, hypotension, elevated plasma norepinephrine, and symptoms of orthostatic intolerance provoked by assumption of an upright posture. We studied a woman with severe progressive SOH with blood pressure unresponsive to the pressor effects of alpha(1)-adrenergic receptor (AR) agonists. We tested the hypothesis that a circulating factor in this patient interferes with vascular adrenergic neurotransmission. Preincubation of porcine pulmonary artery vessel rings with patient plasma produced a dose-dependent inhibition of vasoconstriction to phenylephrine in vitro, abolished vasoconstriction to direct electrical stimulation, and had no effect on nonadrenergic vasoconstrictive stimuli (endothelin-1), PGF-2alpha (or KCl). Preincubation of vessels with control plasma was devoid of these effects. SOH plasma inhibited the binding of an alpha(1)-selective antagonist radioligand ([(125)I]HEAT) to membrane fractions derived from porcine pulmonary artery vessel rings, rat liver, and cell lines selectively overexpressing human ARs of the alpha(1B) subtype but not other AR subtypes (alpha(1A) and alpha(1D)). We conclude that a factor in SOH plasma can selectively and irreversibly inhibit adrenergic ligand binding to alpha(1B) ARs. We propose that this factor contributes to a novel pathogenesis for SOH in this patient. This patient's syndrome represents a new disease entity, and her plasma may provide a unique tool for probing the selective functions of alpha(1)-ARs.

Case Reports↗