Laser Doppler Flowmeter Signal Research Articles

Characterization of forehead blood flow bias on NIRS signals during neural activation with a verbal fluency task

The major problem of near-infrared spectroscopy (NIRS) for brain activity measurement during verbal fluency task is the overlapping forehead scalp blood flow (FBF) on the target cerebral blood flow (CBF). There could be among-individual differences in the influence of FBF on CBF. We investigated effects of FBF on CBF by comparing signals obtained through a laser Doppler flowmeter (LDF) and NIRS using the modified Beer-Lambert Law (MBLL). Among 25 healthy individuals, 7 participants showed a strong correlation between LDF and NIRS signals (rs >0.500). There were no significant differences according to age or sex. Subsequently, we applied the hemodynamic separation method to the values calculated using the MBLL (Δ[oxy-Hb]M): to separate the concentration of oxygenated hemoglobin in the forehead (Δ[oxy-Hb]F) and cerebral cortex (Δ[oxy-Hb]C). First, we found that the influence of Δ[oxy-Hb]F on Δ[oxy-Hb]C in the high rs group was almost twice as large as that in the low rs group. Second, presence of sex and age differences in the influence of Δ[oxy-Hb]F on Δ[oxy-Hb]C were suggested. Based on the results, we discuss the factors affecting FBF and the resulting variations in NIRS signals.

A new approach to the analysis of skin blood flow oscillations in human

It is considered that there are six non-overlapping frequency intervals with constant boundaries. These intervals correspond to different mechanisms of skin blood flow regulation. The boundaries do not depend on functional conditions but this statement should be verified. Also it remains unclear how the oscillatory components of skin blood flow are related. Thus the study is aimed to verify statistically the boundaries of frequency intervals, to test the hypothesis that the boundaries depend on age and to search for relationships between spectral components of skin blood flow. The study involved 105 healthy volunteers aged from 20 to 65 years, which were divided into two age groups. Skin blood flow was registered with laser Doppler flowmeter (LDF). Assessments of frequency interval boundaries and relationship between the frequency oscillatory components of blood flow were conducted with histogram approach, bootstrap method and correlation analysis. New frequency interval boundaries were found. They were different in two groups. A linear correlation and frequency areas with moderate (0.5–0.7) and high (>0.7) correlation coefficients were found between spectral components of blood flow. The dependence of these correlations on the age was shown. Thus we proposed a conceptually new approach to analysis of spectral components of skin microhemodynamics and interpretation of results obtained by laser Doppler techniques. This approach is the result of the development of modern understanding of relationships between skin blood flow regulation mechanisms and spectral components of LDF signals. It allows one to have a new look at these relationships as well as demonstrates their dependence on the functional state of the organism as a whole.

Microvascular functions in patients with fibromyalgia syndrome: effects of physical exercise.

This study aims to evaluate the current state of microvascular function and to investigate the effect of supervised aerobic exercise on microvascular control mechanisms and health outcomes in women with fibromyalgia syndrome (FMS). Forty female patients (mean age 51±11 years) with a diagnosis of FMS according to the American College of Rheumatology criteria and 20 healthy female controls (mean age 52±9 years) were included in the study. Microvascular blood flow was measured using a laser Doppler flowmeter (LDF) at the volar skin site of the forearm. Pain severity and FMS were assessed using the visual analog scale (VAS) and Fibromyalgia Impact Questionnaire (FIQ), respectively, both at the beginnig and at the end of the study. Fibromyalgia was evaluated and a spectral analysis of LDF signals was carried out to assess the relative contribution of each control mechanisms. The local thermal hyperemia was used to test the microvascular functions. Moderate-intensity aerobic activity (energy expenditure 3.0 to 6.0 metabolic equivalent) was performed by treadmill walking for 30 min for five days each week for a month. The patients with FMS had lower VAS and FIQ scores at the end of the exercise period. There was a positive correlation between improved myogenic and neurogenic mechanisms and reduced FIQ scores. Cardiac signals were positively correlated with the FIQ scores at the end of the exercise period. Endothelial function was under the influence of pain, and baseline nitric oxide activity was found to be positively correlated with VAS. Our study results suggest that microvascular functions are impaired in FMS patients and moderate exercise training is effective to improve the FIQ/VAS scores and enhance vascular functions.

Comparative study of the upper and lower limb skin blood flow control mechanisms in patients with essential hypertension

To investigate limb specific differences in cutaneous vascular function in patients (n=33) with essential hypertension (EHT). In this observational cross-sectional study, baseline skin blood flow and the response to local heating were measured with a laser Doppler flowmeter (LDF) from the volar region of the forearm and the gaiter area of the foot at supine rest. The fractal analysis, detrended fluctuation analysis (DFA), was used to calculate the correlation properties of skin blood flow, LDF signal. The paired t-test and repeated measures ANOVA were used to determine the response to local heating and compare the scaling exponents of different anatomical locations respectively. We found three linear scaling regions that describe the fractal behavior of LDF signal with their slopes, scaling exponents. For cardiac (α(C)) and cardio-respiratory (α(CR)) scaling exponents, thermal hyperemia (T) induced greater change in the leg (α(C)=1.49 ± 0.26; α(CT)=1.62 ± 0.20 p<0.01 and α(CR)=0.84 ± 0.29 α(CRT)=0.42 ± 0.28 p<0.001) than in forearm (α(C)=1.28 ± 0.13; α(CT)=1.33 ± 0.13 p>0.05 and α(CR)=0.73 ± 0.15; α(CRT)=0.65 ± 0.018 p<0.05). Local scaling exponents (α(L) ≈ α(LT) ~ 1) were not significantly different (p>0.05) and, local lines did not shift in parallel with local heating in both extremities. The results of the present study suggest that skin microvascular function is impaired in both extremities in EHT patients. However, myogenic response is not uniform in both extremities and pronounced response to local thermal hyperemia has been observed in the gaiter area compared with the volar region. Further studies are needed to determine if these limb specific microvascular differences is the result of posture-induced structural and functional adaptation.

A NIRS–fMRI investigation of prefrontal cortex activity during a working memory task

Near-infrared spectroscopy (NIRS) is commonly used for studying human brain function. However, several studies have shown that superficial hemodynamic changes such as skin blood flow can affect the prefrontal NIRS hemoglobin (Hb) signals. To examine the criterion-related validity of prefrontal NIRS-Hb signals, we focused on the functional signals during a working memory (WM) task and investigated their similarity with blood-oxygen-level-dependent (BOLD) signals simultaneously measured by functional magnetic resonance imaging (fMRI). We also measured the skin blood flow with a laser Doppler flowmeter (LDF) at the same time to examine the effect of superficial hemodynamic changes on the NIRS-Hb signals. Correlation analysis demonstrated that temporal changes in the prefrontal NIRS-Hb signals in the activation area were significantly correlated with the BOLD signals in the gray matter rather than those in the soft tissue or the LDF signals. While care must be taken when comparing the NIRS-Hb signal with the extracranial BOLD or LDF signals, these results suggest that the NIRS-Hb signal mainly reflects hemodynamic changes in the gray matter. Moreover, the amplitudes of the task-related responses of the NIRS-Hb signals were significantly correlated with the BOLD signals in the gray matter across participants, which means participants with a stronger NIRS-Hb response showed a stronger BOLD response. These results thus provide supportive evidence that NIRS can be used to measure hemodynamic signals originating from prefrontal cortex activation.

Exogenous Zinc Improves Blood Fluidity But Has No Effect on the Mechanisms of Vascular Response to Acetylcholine Iontophoresis in Humans

Recent findings in cellular signaling function of zinc through the mobilization intracellular calcium or by inducing ATP release suggest that extracellular zinc plays an important role in many physiological functions. However, such an extracellular signaling action of zinc for most cells is not known. Therefore, we investigated whether zinc plays any role in endothelium- dependent acetylcholine (ACh)-induced vasodilatation in microvascular beds. Transdermal iontophoresis was used to transport ACh through the forearm skin and cutaneous perfusion was measured using a laser Doppler flowmeter (LDF). Experiments were repeated using (1) zinc instead of ACh to test the effect of zinc ions alone and (2) concomitant iontophoresis of ACh and zinc to explore the effect of zinc on ACh-induced vasodilatation. Although zinc augments blood flow, curve-fitting to LDF signals indicate that zinc has no effect on the neural and endothelial component of ACh-induced vasodilatation. Additionally, no effect of Zn2+ on blood flow was found during its iontophoresis alone. Therefore, it is suggested from the Fourier analysis of LDF signals that the Zn+ might influence blood fluidity by its action on red blood cells deformability/ aggregability during a high-blood-flow condition, which might, in turn, decrease blood viscosity and improve blood flow in vivo.

Evaluation of forearm microvascular blood flow regulation by laser Doppler flowmetry, iontophoresis, and curve analysis: contribution of axon reflex

The relative contribution of vasodilating factors to the control of blood flow in the forearm cutaneous microcirculation is not well defined. Therefore, a mathematical transformation is introduced to decompose the superimposed signal and to investigate the involved mechanisms separately. Transdermal iontophoresis was used for the delivery of acetylcholine (ACh) or sodium nitroprusside (SNP) into the forearm, and cutaneous perfusion was measured using a laser Doppler flowmeter (LDF). The curve fitting procedure used in this study indicates that the LDF signal in response to ACh iontophoresis can be described by the superposition of two independent hyperbolic response curves. Obviously, each component of LDF signal indicates the existence of a separate mechanism, with corresponding rate constant k, latency T, and the saturation level F max. Blockade of C-fiber function (axon reflex) with topical anesthesia removes one of the two components of this response and allows the precise quantification of its contribution. SNP-evoked response also has two components, but their parameters were different from those of ACh. Therefore, ACh and SNP cause vasodilation in the skin microcirculation through different pathways. These findings have implications for clinical studies that use the iontophoresis technique for assessing vascular function and comparing responses to ACh and SNP to evaluate endothelial dysfunction.

Effect of wavelength and bandwidth on the clinical reliability of laser Doppler recordings.

The aim of this study was to investigate the effect of wavelength and bandwidth on laser Doppler flowmeter signals from vital and root-filled teeth, and to establish their sensitivity and specificity. Twenty human subjects were recruited, each with a vital tooth and the contralateral tooth root filled but not restored apart from the palatal access cavity. Readings were taken from these teeth for 3 min at 20 Hz for each of 3.1 kHz, 14.9 kHz and 22.1 kHz bandwidths using a modified laser Doppler blood flow monitor which permitted simultaneous recording using 810 nm and 633 nm light sources with a probe of four optical fibres with 0.25 mm separation. Ten traces from each combination of variables was examined by 10 trained observers who indicated if the traces came from vital or root-filled teeth judged by the amplitude and regularity of pulsatility of the trace. From the accuracy of their replies, sensitivity and specificity were calculated. Median flux values were higher for vital teeth than for root-filled teeth and for the 810 nm wavelength than for the 633 nm wavelength. Flux values increased with wider bandwidth using the 810 nm light source. With the 633 nm light source, the highest flux values were recorded using the 3.1 kHz bandwidth. Using the Mann-Whitney U test, there was a highly significant difference between readings from vital and root-filled teeth for the 3.1 kHz/810 nm wave length combination (p<0.003) and a significant difference for the 3.1 kHz/633 nm wavelength group (p<0.02). Comparison of other groups showed no significant difference (p>0.05). The 810 nm wavelength showed good sensitivity but poor specificity at 14.9 and 22.1 kHz bandwidths. The 633 nm wavelength showed good specificity, but poor sensitivity, at 14.9 and 22.1 kHz bandwidths. The 3.1 kHz bandwidth showed the best sensitivity and specificity for both wavelengths. Sensitivity and specificity were increased if the results of fast Fourier analysis were considered in addition to observations of flux values and pulsatility of traces. The 810 nm/3.1 kHz combination offered the greatest sensitivity and specificity as a test to distinguish between root-filled and vital teeth. This combination was best when the results of Fourier analysis were considered in addition to visual observations.

Beta-adrenergic mechanisms in the nasal mucosa vascular bed.

In thiopentone-anesthetized mature pigs (n = 7), local intra-arterial infusion of the beta 2-adrenoceptor agonists terbutaline and salbutamol and the beta 3-agonist BRL 37344 induced dose-dependent increases in nasal arterial blood flow (BF) and volume of the nasal mucosa (reflecting capacitance vessel function). Increases were also found in the laser Doppler flowmeter signal, reflecting superficial mucosal BF. In contrast to terbutaline and salbutamol, BRL 37344 showed marked effects on volume. Pretreatment with the beta-adrenoceptor blocker propranolol significantly reduced the vasodilatory effects of terbutaline and salbutamol, whereas the BF increase evoked by BRL 37344 was not affected. Exogenous noradrenaline (NA) induced in vitro dose-dependent contractions of human nasal mucosa biopsies obtained from patients with non-allergic chronic rhinitis (n = 21) or non-allergic nasal polyposis (NANP, n = 16). On a molar basis, the contractile effect of NA was significantly greater in nasal mucosa samples without histological abnormalities when compared to biopsies with abundant inflammatory cells and edema within the submucosa. In the presence of propranolol, the vasoconstrictor effect of NA was significantly enhanced in biopsies with abundant inflammatory cells obtained from patients with NANP (P < 0.01). This observation suggests the possible occurrence of a beta 2 hyper-reactivity in the nasal mucosa of patients with NANP. After precontraction in a Krebs-Ringer solution with 50 nM K+, all nasal biopsies studied showed dose-dependent relaxation to terbutaline, salbutamol and BRL 37344. This relaxant effect was markedly reduced after pretreatment with propranolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Cochlear blood flow measured by averaged laser Doppler flowmetry (ALDF)

This report describes a new approach to estimate the hydromechanical properties of a vascular system. Averaged laser Doppler flowmetry (ALDF) was developed by averaging the flux signal of a laser Doppler flowmeter (LDF) synchronized to the heart cycle. The usefulness of this method was verified by manipulation of the cochlear microvasculature. Twelve pigmented guinea pigs under pentobarbital/fentanyl anesthesia were used. The cochlea was surgically exposed and the LDF probe placed on the bony surface of the first turn to monitor cochlear blood flow (CBF). The LDF flux signal (0.2 s time constant) was sampled by an A/D board at 2 kHz for 255 ms and averaged with synchronization to the heart beat. The mean blood flow, peak to peak amplitude, and time (phase) delay of pulsatile flow were measured from the averaged signal. According to a transmission line model of the vascular system, under a given perfusion pressure, mean flow reflects resistance while amplitude and time delay of the pulsatile flow are related to the reactance component of the impedance of the vascular system. During the formation of photochemically-induced thrombosis in the cochlear microvasculature, there was a dramatic mean flux decrease (90.1 ± 3.4% from baseline (BL), N = 6). Additionally, a time-dependent decrease in amplitude and time delay of pulsatile flow were indicated by ALDF. These results suggest a large increase in vascular resistance and significant decrease in compliance. After application of 2% sodium nitroprusside (NP) to the round window membrane, mean flux increased by 78.3 ±17.6% BL; amplitude and time delay of pulsate blood flow increased by 81.0 ± 14.6% ( N = 6) and 11.5 ± 3.2 ms ( N = 6), respectively. These changes can be interpreted as lowered resistance and increased compliance consistent with vasodilatation by NP. ALDF is a new method which derives additional information from the LDF signal. The new information provided by ALDF can be of importance in assessment of basic cochlear microcirculation and interpretation of peripheral vascular diseases in the cochlea and other organs.

Noncholinergic, nonadrenergic cortical vasodilatation elicited by thalamic centromedian-parafascicular complex.

The centromedian-parafascicular complex (CMPf) of the intralaminar thalamus was stimulated in anesthetized, ventilated rats, and cerebral cortical perfusion was continuously measured using laser Doppler flowmetry. Stimulation led to a frequency- and intensity-dependent increase in cortical perfusion (vasodilatation). The maximum response was seen at a rate of 200/s, and studied at 150 microA, was a 120 +/- 27% (n = 6) increase in flow. The mean time from the initiation of stimulation to a change in the cerebral blood flow measured by laser Doppler flowmeter signal was 800 +/- 100 ms (n = 13). The response to electrical stimulation was not blocked after high spinal cord section. Chemical stimulation of the CMPf neurons by microinjection of carbachol led to a 98 +/- 15% (n = 4) increase in flow. The response to electrical stimulation was not blocked by the muscarinic antagonist scopolamine (1 mg/kg) or by the nicotinic antagonist mecamylamine (4 mg/kg). It was also unaffected by the beta-adrenoceptor antagonist propranolol (1.5 mg/kg). These data add to understanding of the CMPf cerebral vasodilator response by demonstrating a robust stimulus-locked change in cortical perfusion that does not involve a cholinergic or adrenergic mechanism. It is also shown to be frequency and intensity dependent, consistent with a functioning physiological system, and has a rapid onset consistent with a primarily neurally mediated phenomenon. Furthermore, it is elicited by pathways that may possibly be entirely within the central nervous system and is due to activation of cell bodies within the region.

Gender Differences in Facial Skin Blood Perfusion during Basal and Heated Conditions Determined by Laser Doppler Flowmetry

The major problem of near-infrared spectroscopy (NIRS) for brain activity measurement during verbal fluency task is the overlapping forehead scalp blood flow (FBF) on the target cerebral blood flow (CBF). There could be among-individual differences in the influence of FBF on CBF. We investigated effects of FBF on CBF by comparing signals obtained through a laser Doppler flowmeter (LDF) and NIRS using the modified Beer-Lambert Law (MBLL). Among 25 healthy individuals, 7 participants showed a strong correlation between LDF and NIRS signals (rs >0.500). There were no significant differences according to age or sex. Subsequently, we applied the hemodynamic separation method to the values calculated using the MBLL (Δ[oxy-Hb]M): to separate the concentration of oxygenated hemoglobin in the forehead (Δ[oxy-Hb]F) and cerebral cortex (Δ[oxy-Hb]C). First, we found that the influence of Δ[oxy-Hb]F on Δ[oxy-Hb]C in the high rs group was almost twice as large as that in the low rs group. Second, presence of sex and age differences in the influence of Δ[oxy-Hb]F on Δ[oxy-Hb]C were suggested. Based on the results, we discuss the factors affecting FBF and the resulting variations in NIRS signals.

Measurement of hepatic perfusion in rats by laser Doppler flowmetry.

Little is known about the performance of the laser Doppler flowmeter (LDF) with changes in flow characteristics in the hepatic microcirculation. Red blood cell (RBC) flux, as measured by LDF, is sensitive to alterations in RBC velocity and RBC concentration, and both parameters must be considered when evaluating the technique. In vitro, linearity of LDF signal with RBC velocity up to 4 mm/s (r greater than 0.99) and RBC volume fractions up to 1.5% were demonstrated (r greater than 0.98). At higher velocities and volume fractions, RBC flux was underestimated. In portally perfused rat liver, LDF output was linearly related to total liver blood flow (TLBF; r greater than 0.9) for perfusate hematocrits between 2.5 and 40%, although the slope varied between preparations. At constant TLBF (2 ml.min-1.g-1), the LDF output changed linearly with perfusate hematocrit up to 20% (r greater than 0.99) but underestimated the increase at 40%. These results suggest that the LDF responds linearly to velocity-mediated flow changes but that it may underestimate a change if mediated through alteration in tissue RBC concentration. With hepatic nerve stimulation, TLBF fell to 51 +/- 14% of prestimulation (P less than 0.001), whereas the LDF output and superficial flow measured by 85Kr clearance fell to 12 +/- 10 and 14 +/- 10% (both P less than 0.01 vs. TLBF), respectively, suggesting that the LDF may be used to follow rapid flow changes in the periphery of the liver.

Methylene blue attenuates vasodilatation and enhances vasoconstriction in response to endothelin‐1 in the pig nasal mucosa

In thiopentone anaesthetized pigs (n = 10), simultaneous recordings of the vasomotor response to local intra-arterial infusion of endothelin-1 and -3 were performed in three different vascular compartments of the nasal mucosa. Sphenopalatine artery blood flow (reflecting nasal blood flow), nasal cavity volume (representing blood content in capacitance vessels) and laser Doppler flowmeter signal (reflecting superficial mucosal blood flow) increased in response to low doses (4 x 10(-9) to 4 x 10(-8) moles) of endothelin-1. In contrast, marked vasoconstriction (up to 50% of arterial blood flow reduction) occurred upon higher doses (4 x 10(-7) to 4 x 10(-6) moles). Endothelin-3 (4 x 10(-9) to 4 x 10(-6) moles) evoked at the highest dose a long-lasting increase of systemic arterial blood pressure resulting in a 22 +/- 4% increase in nasal vascular resistance. After local intra-arterial pretreatment with methylene blue (4 x 10(-4) mol), the vasodilatory responses to low doses of endothelin-1 were abolished for the three vascular parameters studied, whereas the vasoconstrictor responses in resistance and capacitance vessels evoked by higher doses of endothelin-1 were increased. In contrast, the laser Doppler flowmeter signal reduction in response to endothelin-1 was markedly attenuated. The vasodilatatory effect of substance P was abolished after methylene blue probably due to interference with effects of endothelium dependent relaxing factor (EDRF). These observations suggest that in the pig nasal mucosa in vivo, exogenous endothelin-1 induces a dose-dependent reduction of blood flow in resistance and capacitance vessels and in superficial mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

Responses of bone and joint blood vessels in cats and rabbits to electrical stimulation of nerves supplying the knee.

1. Experiments were performed to assess the extent to which knee joint blood flow in cats and rabbits is affected by electrical stimulation of the nerve supply to the knee. 2. Absolute changes in blood flow were measured using the radiolabelled microsphere (approximately 15 microns) technique whilst relative changes in blood flow were assessed using laser Doppler flowmetry. 3. Despite deep general anaesthesia, sympathetic nerve fibres innervating cat knee joint blood vessels showed marked 'tone'. 4. Blood flow to the joint capsule (synovium and overlying fibrous and areolar tissues) was substantially reduced (by approximately 90% in the cat and approximately 45% in the rabbit) during electrical stimulation of the articular nerve supply. 5. The percentage change in the laser Doppler flowmeter signal did not differ significantly from the percentage change in blood flow measured by microsphere technique. 6. Blood vessels in the cancellous bone of the distal femur (condyles) and proximal tibia (plateau) appear to be innervated by vasoconstrictor fibres which reach their effectors via the articular nerves. However, the cortical bone and red marrow of the diaphysis of the femur do not receive such innervation. 7. The potency of the vasoconstrictor influences acting on joint blood vessels could be of relevance in the pathogenesis of inflammatory joint diseases.

Sympathetic vascular control of the pig nasal mucosa (III): Co-release of noradrenaline and neuropeptide Y.

The overflows of noradrenaline (NA) and neuropeptide Y like immunoreactivity (NPY-LI) and vascular responses upon sympathetic nerve stimulation were analysed in the nasal mucosa of pentobarbital anaesthetized pigs. In controls, a frequency-dependent increase in NA overflow was observed whereas detectable release of NPY-LI occurred only at 6.9 Hz. Parallel decreases in blood flow in the sphenopalatine artery and vein and in nasal mucosa volume (reflecting blood volume in the venous sinusoids) were observed. The laser Doppler flowmeter signal (reflecting superficial blood flow) increased upon low and decreased upon high frequency stimulation. Twenty-four hours after reserpine pretreatment and preganglionic decentralization, the NA overflow was abolished while a frequency-dependent release of NPY-LI occurred. Forty, 60 and 80% of the vasoconstrictor responses then remained upon stimulation with a single impulse, 0.59 and 6.9 Hz, respectively. Both the vasoconstriction and NPY-LI overflow, however, were subjected to fatigue upon repeated stimulation. In reserpinized animals release of NPY-LI and vasoconstrictor responses were larger upon stimulation with irregular bursts at 0.59 Hz compared to effects seen at stimulation with continuous impulses. Pre-treatment with the alpha-adrenoceptor antagonist phenoxybenzamine or the monoamine reuptake inhibitor, desipramine, enhanced NA overflow by 2-3 and 1.5 times at 0.59 and 6.9 Hz, respectively. Phenoxybenzamine significantly reduced the nerve-evoked vascular responses while the release of NPY-LI at 6.9 Hz was increased. Desipramine increased the functional responses but reduced the NPY-LI overflow. During tachyphylaxis to the vasoconstrictor effects of the stable adenosine 5'-triphosphate (ATP) analogue alpha-beta-methylene ATP (mATP) in controls, the vasoconstrictor responses as well as the NA and NPY-LI overflow to nerve stimulation were unmodified. In reserpinized animals, however, the vascular responses and the overflow of NPY-LI were reduced after mATP tachyphylaxis. These data show that both NA and NPY are released upon sympathetic nerve stimulation in the nasal mucosa in vivo and this release seems to be regulated via prejunctional alpha-adrenoceptors. The lack of effect of mATP tachyphylaxis under control conditions makes it less likely that ATP serves as a major mediator of the large nonadrenergic vasoconstrictor component.