Effects of mirogabalin, a novel ligand for the α2δ subunit of voltage-gated calcium channels, on N-type calcium channel currents of rat dorsal root ganglion culture neurons.

Mirogabalin, which is a novel ligand for the α2δ subunit of voltage-gated calcium channels, is being developed for treating neuropathic pain including diabetic peripheral neuropathy and postherpetic neuralgia. Mirogabalin possesses unique α2δ subunit binding characteristics and has potent and long-lasting analgesic effects in neuropathic pain models. In the present study, we investigated the effects of mirogabalin on N-type calcium channel currents of the rat dorsal root ganglion (DRG) culture neurons using the whole-cell patch clamp technique. Small or medium DRG neurons were isolated from Sprague-Dawley rats and were incubated for 20 to 24 h with mirogabalin or pregabalin. The DRG neurons were depolarised from a holding potential of -40 mV to +40 mV in steps of 10 mV for 220 ms, and elicited N-type calcium channel currents were recorded. The N-type calcium channel currents were verified by sensitivity to ω-conotoxin GVIA, a selective N-type calcium channel blocker. Mirogabalin inhibited the calcium channel currents of rat DRG neurons at 50 µM, and pregabalin inhibited them at 200 µM. Mirogabalin and pregabalin showed significant differences in the peak current densities at depolarisation to -20 and -10 mV when compared with that shown by the vehicle control. In conclusion, mirogabalin inhibits N-type calcium channel currents in rat DRG culture neurons. The potent and long-lasting analgesic effects of mirogabalin are thought to be associated with its potent and selective binding to α2δ-1 subunits and following functional inhibition of calcium channel currents.

Construction and usability of community health nursing database in rural north-eastern Thailand.

INTRODUCTIONS: Digitization could be incorporated in rural areas of resource-poor countries because information gathered by nurses working on-site could be better used. BACKGROUND: For effective management of community health information, the usage and maintenance of digital records are important. Digitization of information provides essential information for informing health policy. AIM: To develop a sustainable database to effectively collect and manage community health information and nursing practice. METHODS: This study used a mixed method design. Phase 1 involved the development of a database system through repeated systematic focus group discussions with community health nurses. Phase 2 involved a practical trial examination of the developed system with both objective and subjective evaluations. RESULTS: A nursing database system was developed with templates designed for the major health problems of communities. The templates were composed of multiple-choice items and a free-text field that allowed records to be more detailed than handwritten records and maintained in standardized formats. This enables accumulation of data that were less likely to be influenced by the variance of ability in each nurse. DISCUSSION AND CONCLUSION: A multifaceted evaluation of the database system suggested that it could improve the efficiency of information management and contribute to the improvement of nursing care quality through standardization of the recording pattern. IMPLICATIONS FOR NURSING AND HEALTH POLICY: The nursing database will enable high-quality information storage that will potentially better inform health and healthcare policies as well as enable visualization of data concerning nursing care challenges and activities within the relevant communities. This information is essential for policy development and implementation in areas of human and fiscal resource allocations and meeting training/education needs.

Relationship between perceived softness of bilayered skin models and their mechanical properties measured with a dual-sensor probe.

The development of a sensor system that can predict the subjective softness of human skin is an important goal for the cosmetics industry. Here, we first carried out a subjective softness evaluation test using 65 skin models consisting of polyurethane bilayers with different thickness of the superficial layer and different degree of cross-polymerization of the basal layer. The results showed that perceived softness was dependent on the mechanical properties of both the superficial and basal layers. Then, we used a recently developed tactile sensor system composed of a piezoelectric tactile sensor and a load cell to measure mechanical softness parameters of the superficial layer and the whole model, respectively. Statistical analysis showed that the data obtained from these two sensors were well correlated with the perceived softness of the prepared models. These results suggest that it may be feasible to predict the subjective softness of human skin in vivo from non-invasive mechanical softness measurements of the superficial skin layer and whole skin obtained with our new dual-probe sensor system.

Value of plasma B type natriuretic peptide measurement for heart disease screening in a Japanese population.

BACKGROUND: Conflict exists regarding the usefulness of measuring plasma B type natriuretic peptide (BNP) concentrations for identifying impaired left ventricular (LV) systolic function during mass screening. Various cardiac abnormalities, regardless of degree of LV dysfunction, are prone to carry a high risk of cardiovascular events. OBJECTIVE: To examine the validity of plasma BNP measurement for detection of various cardiac abnormalities in a population with a low prevalence of coronary heart disease and LV systolic dysfunction. DESIGN AND SETTING: Participants in this cross sectional study attended a health screening programme in Iwate, northern Japan. Plasma BNP concentrations were determined in 1098 consecutive subjects (mean age 56 years) by direct radioimmunoassay. All subjects underwent multiphasic health checkups including physical examination, ECG, chest radiography, and transthoracic echocardiography. RESULTS: Conventional diagnostic methods showed 39 subjects to have a wide range of cardiac abnormalities: lone atrial fibrillation or flutter in 11; previous myocardial infarction in seven; valvar heart disease in seven; hypertensive heart disease in six; cardiomyopathy in six; atrial septal defect in one; and cor pulmonale in one. No subjects had a low LV ejection fraction (< 40%). To assess the utility of plasma BNP measurement for identification of such patients, receiver operating characteristic analysis was performed. The optimal threshold for identification was a BNP concentration of 50 pg/ml with sensitivity of 89.7% and specificity of 95.7%. The area under the receiver operating characteristic curve was 0.970. The positive and negative predictive values at the cutoff level were 44.3% and 99.6%, respectively. CONCLUSION: Measurement of plasma BNP concentration is a very efficient and cost effective mass screening technique for identifying patients with various cardiac abnormalities regardless of aetiology and degree of LV systolic dysfunction that can potentially develop into obvious heart failure and carry a high risk of a cardiovascular event.

SEA0400, a novel and selective inhibitor of the Na+-Ca2+ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models.

The effect of the newly synthesized compound 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400) on the Na+-Ca2+ exchanger (NCX) was investigated and compared against that of 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea (KB-R7943). In addition, the effects of SEA0400 on reperfusion injury in vitro and in vivo were examined. SEA0400 was extremely more potent than KB-R7943 in inhibiting Na+-dependent Ca2+ uptake in cultured neurons, astrocytes, and microglia: IC50s of SEA0400 and KB-R7943 were 5 to 33 nM and 2 to 4 microM, respectively. SEA0400 at the concentration range that inhibited NCX exhibited negligible affinities for the Ca2+ channels, Na+ channels, K+ channels, norepinephrine transporter, and 14 receptors, and did not affect the activities of the Na+/H+ exchanger, Na+,K+-ATPase, Ca2+-ATPase, and five enzymes. SEA0400, unlike KB-R7943, did not inhibit the store-operated Ca2+ entry in cultured astrocytes. SEA0400 attenuated dose- dependently paradoxical Ca2+ challenge-induced production of reactive oxygen species, DNA ladder formation, and nuclear condensation in cultured astrocytes, whereas it did not affect thapsigargin-induced cell injury. Furthermore, administration of SEA0400 reduced infarct volumes after a transient middle cerebral artery occlusion in rat cerebral cortex and striatum. These results indicate that SEA0400 is the most potent and selective inhibitor of NCX, and suggest that the compound may exert protective effects on postischemic brain damage.

Brain natriuretic peptide and cardiac rupture after acute myocardial infarction.

Cardiac rupture is a fatal complication in the acute stage of myocardial infarction (MI). However, no measures have yet been established to predict it. Herein we describe three MI patients with cardiac rupture in whom plasma brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) concentrations had been serially monitored from the onset of MI to cardiac rupture. In these cases, plasma BNP levels increased without symptomatic and hemodynamic changes and reached their highest level immediately before cardiac rupture, while plasma ANP levels remained unchanged. These cases suggest that the increased plasma BNP concentrations without symptomatic and hemodynamic changes may be a useful marker for predicting cardiac rupture after acute MI.

Blunted peripheral vasodilatory response is a hallmark of progressive deterioration in mild to moderate congestive heart failure.

BACKGROUND: Several reports have shown that dilatory response to acetylcholine (ACh) and nitroprusside (SNP) is blunted in the limb vasculature in patients with congestive heart failure (CHF). However, it is not yet known whether this vascular dysfunction is related to clinical outcome. We have examined the relationship between peripheral vasodilatory response and prognosis of CHF. METHODS AND RESULTS: A total of 46 patients with mild to moderate CHF were enrolled (mean age 56 years). Changes in forearm blood flow (FBF) during intra-arterial infusion of ACh and SNP were determined by plethysmography. FBF changes above baseline for each dose were cumulated and used as an index of endothelium-dependent (ACh) response and endothelium-independent (SNP) response, respectively. During the follow-up period (mean 32 months), 9 patients were admitted to the hospital for treatment of worsening refractory CHF, and 6 patients died suddenly or developed life-threatening arrhythmia. By Kaplan-Meier analysis, when all cardiac events were included, no significant differences were observed between any levels of vascular response in terms of prognosis. However, when deterioration events were analyzed separately, patients with SNP responses below the median (7.4 mL/min/dL) had significantly higher rates of hospital admission caused by worsening CHF than those with above the median responses (P <.05). This relationship was not found between ACh response and clinical outcome. By Cox multivariate analysis, blunted vasodilatory response to SNP was a significant predictor of worsening CHF (chi(2) = 3.95; P <.05). CONCLUSION: This study has shown that patients with mild to moderate CHF showing a blunted vascular response to SNP rather than ACh were admitted to the hospital more frequently because of deterioration of CHF. This finding suggests that changes in vascular smooth muscle and/or vascular structure in the peripheral vasculature may be a critical element in the worsening of CHF.

KB-R7943 inhibits store-operated Ca(2+) entry in cultured neurons and astrocytes.

We have studied cyclopiazonic acid (CPA)-sensitive store-operated Ca(2+) entry (SOCE) in cultured neurons and astrocytes and examined the effect of 2-[2-[4-(4-nitrobenzyloxy)phenyl]]isothiourea (KB-R7943), which is often used as a selective inhibitor of the Na(+)-Ca(2+) exchanger (NCX), on the SOCE. CPA increased transiently intracellular Ca(2+) concentration ([Ca(2+)](i)) followed by a sustained increase in [Ca(2+)](i) in neurons and astrocytes. The sustained increase in [Ca(2+)](i) depended on the presence of extracellular Ca(2+) and inhibited by SOCE inhibitors, but not by a Ca(2+) channel inhibitor. CPA also caused quenching of fura-2 fluorescence when the cells were incubated in Mn(2+)-containing medium. KB-R7943 at 10 microM inhibited significantly CPA-induced sustained increase in [Ca(2+)](i) in neurons and astrocytes. KB-R7943 also inhibited CPA-induced quenching of fura-2 fluorescence in the presence of extracellular Mn(2+). These results indicate that cultured neurons and astrocytes possess SOCE and that KB-R7943 inhibits not only NCX but also SOCE.

Effects of tumor necrosis factor-alpha on basal and stimulated endothelium-dependent vasomotion in human resistance vessel.

The aim of this study was to determine whether tumor necrosis factor (TNF)-alpha would impair basal and stimulated endothelium-dependent vasomotion in human resistance vessel. Changes in baseline and acetylcholine (ACh)-induced forearm vascular resistance (FVR) were measured plethysmographically before and after a low-dose intraarterial forearm infusion of TNF-alpha according to the following three protocols in healthy volunteers. In the condition without pretreatment, basal FVR was significantly increased by TNF-alpha (from 30.5 +/- 4.8 to 39.9 +/- 5.9 units; p < 0.01), whereas ACh-induced minimal FVR did not differ between pre- and post-TNF-alpha states. In the condition after pretreatment with the cyclooxygenase inhibitor acetylsalicylic acid, although the vascular effects of TNF-alpha on basal FVR appeared to be blocked (37.1 +/- 5.3 vs. 37.6 +/- 5.2; NS), ACh-induced minimal FVR did not differ between pre- and post-TNF-alpha states. In the condition after pretreatment with the nitric oxide (NO) synthase inhibitor N(G)-monomethyl-L-arginine, the vascular effect of TNF-alpha on basal FVR was diminished, and the ACh-induced maximal dilatory response was significantly blunted after TNF-alpha compared with before TNF-alpha (minimal FVR: 30.4 +/- 12.0 vs. 12.3 +/- 4.2 units; p < 0.05). These findings suggest that brief exposure of the human forearm resistance artery to TNF-alpha may increase basal bioavailability of the vasoconstrictor prostaglandin and reduce basal bioavailability of NO. In the stimulated condition, TNF-alpha-induced vascular dysfunction may be overwhelmed by increased NO bioavailability in healthy humans.

Na(+)-Ca(2+) exchanger isoforms in rat neuronal preparations: different changes in their expression during postnatal development.

We examined the relative amounts of Na(+)-Ca(2+) exchanger (NCX) isoform mRNAs in cultured neurons, astrocytes and developmental rat brain. NCX1 transcript was predominant in neurons and astrocytes, but NCX2 transcript was about four-fold higher than NCX1 or NCX3 transcript in adult rat cortex. NCX2 transcript in the cortex increased markedly during postnatal development, whereas NCX1 and NCX3 transcripts decreased. Na(+)-dependent 45Ca(2+) uptake in the cortical homogenate increased significantly during postnatal development.

[The effects of aerobic training on the emotional response in patients who underwent cardiac surgery].

It has been reported that cardiac surgery and aerobic training influence the patient's emotional response. We investigated the changes in emotional response before and after cardiac surgery and during aerobic exercise training as a cardiac rehabilitation using profile of mood states (POMS). Subjects were thirty-five patients (25 men and 10 women, average 57 years) who underwent cardiac surgery. All patients participated in the rehabilitation program which included aerobic exercise training after cardiac surgery. Aerobic training consisted of cycle ergometer or treadmill. Emotional states were evaluated by POMS score at the preoperative phase, early postoperative phase (about 10 days after surgery) and aerobic training (about 20 days after surgery). Most of the emotional state (tension, anxiety, anger and hostility) significantly improved after cardiac surgery. In particular, aerobic training has an additional effect for improving one of the emotional state which is tension and anxiety. However, several factors such as deconditioning, postoperative complications and high age delayed the improving of emotional response.

Time-dependent changes of tissue erythorbic acid concentrations in guinea pigs.

The concentrations of erythorbic acid(ErA) and L-ascorbic acid(AsA) in the tissues of guinea pigs orally administered AsA or ErA were measured over the passage of time using high-performance liquid chromatography. Guinea pigs were each administered 5 mg AsA or 100 mg ErA, and killed at a specified time thereafter. The AsA concentrations in the tissues of AsA-administered guinea pigs and the ErA concentrations in the tissues of ErA-administered guinea pigs increased for 3 h after the respective administrations and decreased thereafter in both groups. The AsA concentration in the tissues of AsA-administered guinea pigs tended to be similar to the sum of AsA and ErA concentrations in the ErA-administered guinea pigs within 3 h after administration.

The Na+-Ca2+ exchange inhibitor KB-R7943 inhibits high K+-induced increases in intracellular Ca2+ concentration and [3H]noradrenaline release in the human neuroblastoma SH-SY5Y.

The effects of the Na+-Ca2+ exchange inhibitor 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea methanesulfonate (KB-R7943) on depolarization-induced Ca2+ signal and [3H]noradrenaline release were examined in SH-SY5Y cells. KB-R7943 at 10 microM significantly inhibited high K+-induced increase in intracellular Ca2+ concentration. KB-R7943 also inhibited high K+-evoked release of [3H]noradrenaline from the cells. These findings suggest that the Na+-Ca2+ exchanger in the reverse mode is involved at least partly in depolarization-induced transmitter release.

Peripheral resistance vessel dysfunction in Marfan syndrome.

BACKGROUND: Patients with Marfan syndrome show a hereditary abnormality of elastin metabolism that may cause aortic enlargement and dissection. We have hypothesized that abnormal elastin may alter peripheral vascular structure and function. METHODS: Forearm blood flow (FBF) (in milliliters per minute per 100 mL) response to the endothelium-dependent dilator acetylcholine (0.75 to 4.5 microg/min per 100 mL), the endothelium-independent dilator sodium nitroprusside (0.05 to 0.3 microg/min per 100 mL), and structure-related maximum dilator response (10-minute occlusion-induced reactive hyperemia) were measured by plethysmograph in 10 patients with Marfan syndrome (mean age 44 years) and 10 healthy age- and sex-matched controls. Patients with the complications of hypercholesterolemia, diabetes mellitus, or heart failure were excluded from the study. RESULTS: Basal FBF (mean +/- SE) did not differ between the 2 groups (2.7 +/- 0.3 vs 2.3 +/- 0.4). Maximum FBF response to acetylcholine in patients with Marfan syndrome was significantly lower than that of healthy controls (8.5 +/- 2.1 vs 15.4 +/- 1.7 mL/min per 100 mL; P <.05). Reactive hyperemia was also lower in patients with Marfan syndrome (at peak 23.0 +/- 2.5 vs 29.5 +/- 2.3 mL/min per 100 mL; P <.05), but sodium nitroprusside-induced FBF changes did not differ between the 2 groups (10.3 +/- 1.1 vs 10.2 +/- 1.5 mL/min per 100 mL; P = not significant). CONCLUSION: These observations suggest that endothelium-dependent dilation and maximum dilator reserve capacity are both abnormal in peripheral resistance vessels of patients with Marfan syndrome. These peripheral vasomotion abnormalities may have a detrimental impact on the cardiovascular system in this disorder.

Increased plasma group II phospholipase A(2) concentrations in patients with acute myocardial infarction: correlation with tumor necrosis factor-alpha.

AIMS: Group II phospholipase A(2) (PLA(2)) is thought to play an important role in inflammation and tissue injury. It has been suggested that the inflammatory process is important in the setting and progression of myocardial ischemia or reperfusion. We measured plasma PLA(2) as well as inflammatory cytokines in patients in the acute stage of myocardial infarction. METHODS AND RESULTS: In 48 patients with acute myocardial infarction, blood samples were taken to measure plasma PLA(2), tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta) 36-48 h after onset. Serial changes in plasma PLA(2) were also examined in 15 consecutive patients in this group. Plasma PLA(2) levels were significantly higher in complicated patients (Killip's class > or = II) than in uncomplicated patients (Killip's class = I) (35.9 +/- 11.9 vs. 5.3 +/- 1.1 ng/ml, p < 0.01). Plasma PLA(2) concentrations increased gradually over time during the first 3 days and at 36-48 h after onset were correlated with left-ventricular ejection fraction on admission (r = -0.42, p < 0.01), and with plasma TNF-alpha (r = 0.39, p < 0.01), but not with IL-1 beta. CONCLUSION: Plasma PLA(2) concentrations rose during the acute stage of myocardial infarction, especially in severe cases mainly with heart failure. TNF-alpha may be associated with PLA(2)activity as a potent stimulator in vivo.

Hepatic branched-chain alpha-keto acid dehydrogenase complex in female rats: activation by exercise and starvation.

The effects of acute exercise and starvation on hepatic branched-chain alpha-keto acid dehydrogenase (BCKDH) complex activity were examined in female rats fed high (30%)- or low (8%)-protein diets. The total activity of the complex was significantly higher in the high protein-fed rats than in the low protein-fed rats but was not affected by acute exercise and starvation in either diet group. The proportion of the active form of BCKDH complex was less than 10% in both diet groups. Acute exercise and starvation markedly increased the active form of the complex in both diet groups. The activity of BCKDH kinase, which is responsible for inactivation of the BCKDH complex by phosphorylation, tended to be decreased by acute exercise and starvation in both diet groups. These results suggest that the activity of the BCKDH kinase is an important factor determining the proportion of the active form of BCKDH complex in exercise and starvation, and that the female rat is a useful model for studying the regulation of hepatic BCKDH complex activity.

Effects of ruminal infusion of volatile fatty acids on plasma concentration of growth hormone and insulin in sheep.

In an initial experiment we observed postprandial changes in plasma concentrations of growth hormone (GH), insulin, glucagon, and somatostatin (SRIF) in sheep. We then examined whether increasing the rumen concentration of volatile fatty acids (VFA) by infusing a VFA mixture at three rates (53.5, 107, and 214 micromol/kg/min for 4 hr) mimicked the postprandial changes in hormone secretion. Feeding significantly (P < 0.05) suppressed the plasma GH concentration for 6 hr, whereas it significantly (P < 0.05) increased plasma concentrations of insulin, glucagon, and SRIF. Plasma glucose levels tended to decrease after feeding but then gradually increased over the prefeeding level (P < 0.05). Intraruminal infusion of the VFA mixture at 107 micromol/kg/min caused similar changes in ruminal VFA concentrations to those seen after feeding. The infusion significantly (P < 0.05) suppressed GH secretion in a dose-dependent manner, whereas it caused a significant (P < 0.05) increase in insulin and glucose concentrations without changing glucagon concentrations. From these results, we conclude that the postprandial change in ruminal VFA concentration may be a physiological signal which modifies GH and insulin secretion in sheep.

Contribution of a high dose of L-ascorbic acid to carnitine synthesis in guinea pigs fed high-fat diets.

Ascorbate is a cofactor of two-enzyme hydroxylation in the pathway of carnitine biosynthesis. The purpose of this study was to investigate the contribution of ascorbate to endogenous carnitine in guinea pigs fed high-fat diets. The contents of carnitine in plasma, urine and tissues of guinea pigs supplemented with L-ascorbic acid were determined and compared with those supplemented with carnitine. Albino-Hartley guinea pigs were fed vitamin C-deficient diets containing lard throughout the experiment. They were administered orally with 5 mg L-ascorbic acid/d/animal for 14 d, and then divided into three groups and administered orally with the following supplements (/d/animal) for 14 d; L (5 mg L-ascorbic acid), LASA (100 mg L-ascorbic acid), and LCAR (10 mg carnitine plus 5 mg L-ascorbic acid). As a control, a normal group was fed vitamin C-deficient diets and administered orally with 5 mg L-ascorbic acid/d/animal for 28 d. The animals fed high-fat diets (L group) had higher free-carnitine contents in the muscle and urine than the normal group. The groups of LCAR and LASA had significantly higher contents of acid-soluble carnitine (p < 0.05) in plasma than the L group. Urinary excretion of carnitine in the LASA group was decreased to the same level as that in the normal group, although no significant difference between the groups of L and LCAR was observed. Moreover, the supplement of ascorbic acid, but not of carnitine, induced a significantly lower content of triacylglycerol in the plasma of the LASA group as compared to the L group (p < 0.05). These data suggest that high doses of ascorbic acid in guinea pigs fed high-fat diets contribute to the enhancement of carnitine synthesis and improvement of the triacylglycerol content in the plasma.

Endothelium-dependent vasodilator response is augmented in peripheral resistance vessels of patients with vasospastic angina.

Although the mechanism underlying coronary conduit artery spasm in vasospastic angina (VAP) remains unknown, coronary endothelial dysfunction has been suggested as playing an important role. However, it remains unknown whether this endothelium-mediated abnormal vasomotion is uniformly evident irrespective of site of vascular bed or vessel size. Plethysmographic studies were carried out to measure changes in forearm resistance vessel blood flow (FBF) induced by acetylcholine (Ach), sodium nitroprusside, and 10-min occlusion-induced reactive hyperemia in 12 patients with VAP, 14 patients with atherosclerotic (>75% fixed stenosis) coronary artery disease (CAD), and 16 healthy controls. FBF responses induced by the endothelium-dependent vasodilator Ach were significantly augmented in patients with VAP compared to controls, whereas this type of FBF response in patients with CAD was significantly blunted (at the maximum dose: VAP, 24.1 +/- 3.0; controls, 17.2 +/- 1.9; CAD, 12.8 +/- 1.9 ml/min per 100 ml; p < 0.01). However, there were no significant differences in FBF responses during infusion of sodium nitroprusside among the three subject groups. Reactive hyperemic FBF which represents maximum vasodilatory capacity did not differ among the three. To assess the role of nitric oxide in the augmented endothelium-dependent response in VAP, Ach-induced FBF response was determined before and after administration of the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine in another VAP group (n = 7). After nitric oxide synthase inhibition, the peak FBF response induced by Ach decreased from 23.3 +/- 3.2 to 14.1 +/- 1.6 ml/min per 100 ml (p < 0.05). In conclusion, the above data suggest that endothelium-dependent vasomotor response to Ach in limb resistance vessels is augmented in patients with vasospastic angina. It seems unlikely that endothelial function is consistently depressed in any area of the vascular bed in this disorder.