The Experts below are selected from a list of 315 Experts worldwide ranked by ideXlab platform
John J Morrison - One of the best experts on this subject based on the ideXlab platform.
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umbilical Artery Tone in maternal obesity
Reproductive Biology and Endocrinology, 2009Co-Authors: Mark P Hehir, Audrey T Moynihan, Siobhan V Glavey, John J MorrisonAbstract:The increasing prevalence of obesity constitutes a major health problem in obstetrics with implications for feto-maternal growth and wellbeing. This study investigated and compared the contractile properties of umbilical arteries excised from obese women, with those excised from women with a normal body mass index (BMI). Sections of umbilical Artery were obtained from umbilical cord samples immediately after delivery and mounted for isometric recording in organ tissue baths under physiological conditions. Cumulative additions of 5-Hydroxytryptamine (5-HT) and Prostaglandin F-2alpha (PgF2alpha) were added in the concentration range of 1 nmol/L to 10 micromol/L. Control vessels were exposed to Krebs physiological salt solution (PSS) only. The resultant effects of each drug addition were measured using the Powerlab hardware unit. 5-HT exerted a significant effect on human umbilical Artery Tone at concentrations of 100 nmol/L, 1 micromol/L, and 10 micromol/L in normal (n = 5; P 0.05). These findings support the hypothesis that endogenous regulation of umbilical Artery Tone is altered in association with maternal obesity. This may be linked to the cardiovascular effects of secretory products of adipose tissue, with implications for the feto-maternal circulation.
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Umbilical Artery Tone in maternal obesity
Reproductive Biology and Endocrinology, 2009Co-Authors: Mark P Hehir, Audrey T Moynihan, Siobhan V Glavey, John J MorrisonAbstract:Background The increasing prevalence of obesity constitutes a major health problem in obstetrics with implications for feto-maternal growth and wellbeing. This study investigated and compared the contractile properties of umbilical arteries excised from obese women, with those excised from women with a normal body mass index (BMI). Methods Sections of umbilical Artery were obtained from umbilical cord samples immediately after delivery and mounted for isometric recording in organ tissue baths under physiological conditions. Cumulative additions of 5-Hydroxytryptamine (5-HT) and Prostaglandin F-2alpha (PgF2alpha) were added in the concentration range of 1 nmol/L to 10 micromol/L. Control vessels were exposed to Krebs physiological salt solution (PSS) only. The resultant effects of each drug addition were measured using the Powerlab hardware unit. Results 5-HT exerted a significant effect on human umbilical Artery Tone at concentrations of 100 nmol/L, 1 micromol/L, and 10 micromol/L in normal (n = 5; P < 0.05) and obese (n = 5; P < 0.05) women. The contractile effect was significantly greater in vessels from obese women {Mean Maximum Tension (MMT) = 4.2532 g} than in those from women of normal BMI (MMT = 2.97 g; P < 0.05). PgF2alpha exerted a significant contractile effect on vessels at 1 micromol/L and 10 micromol/L concentrations when compared with controls (n = 5; P < 0.05). There was a non-significant trend towards an enhanced Tone response in vessels from obese women (MMT = 3.02 g; n = 5), in comparison to vessels from women of a normal BMI (MMT = 2.358 g; n = 5; P > 0.05). Conclusion These findings support the hypothesis that endogenous regulation of umbilical Artery Tone is altered in association with maternal obesity. This may be linked to the cardiovascular effects of secretory products of adipose tissue, with implications for the feto-maternal circulation.
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Umbilcal Artery Tone in maternal obesity
American Journal of Obstetrics and Gynecology, 2006Co-Authors: Mark P Hehir, Audrey T Moynihan, John J MorrisonAbstract:Background The increasing prevalence of obesity constitutes a major health problem in obstetrics with implications for feto-maternal growth and wellbeing. This study investigated and compared the contractile properties of umbilical arteries excised from obese women, with those excised from women with a normal body mass index (BMI).
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Rho A/Rho kinase: human umbilical Artery mRNA expression in normal and pre eclamptic pregnancies and functional role in isoprostane-induced vasoconstriction.
Reproduction, 2006Co-Authors: Anne M. Friel, Donal J. Sexton, Michael O'reilly, Terry J. Smith, John J MorrisonAbstract:Pre eclampsia represents a state of increased or prolonged vasoconstriction, partially linked to the potent vasocontractile effect of isoprostanes. The process of Rho A-mediated calcium sensitisation is inherent to a state of prolonged contractility in many smooth muscle types. The aim of this study was (1) to investigate mRNA expression levels of Rho A and Rho kinase isoforms (I and II) in the umbilical Artery from normotensive and pre eclamptic women and (2) to determine whether the effects of two isoprostanes, 8-iso prostaglandin F 2α (8-iso PGF2α) and 8-iso prostaglandin E 2 (8-iso PGE 2 ), on umbilical Artery Tone, were mediated via the Rho kinase pathway. Real-time RT-PCR using primers for Rho A, ROCK I and ROCK II was performed on total RNA isolated from umbilical Artery specimens obtained from normotensive and pre eclamptic women. The effects of both isoprostanes (n= 6) (in the absence and presence of the specific Rho kinase inhibitor Y-27632), on umbilical Artery Tone were measured, and compared with control recordings. Rho A mRNA expression levels were significantly lower in umbilical Artery samples obtained from pre eclamptic women (n= 4) in comparison to those from normotensive women (n=6) (P 0.05). Both isoprostanes exerted a significant concentration-dependent vasocontractile effect (n=7) (P
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Effects of thrombin, PAR-1 activating peptide and a PAR-1 antagonist on umbilical Artery resistance in vitro
Reproductive Biology and Endocrinology, 2005Co-Authors: Aonghus O'loughlin, Nandini Ravikumar, Crochan J. O'sullivan, Anne M. Friel, John T. Elliott, John J MorrisonAbstract:Background The non-thrombotic effects of thrombin in cardiovascular tissues, as mediated via the protease activated receptors (PARs), and particularly PAR-1, have been the focus of much recent research. The aims of this study were to evaluate the effects of thrombin, a specific PAR-1 activating peptide (PAR1-AP), and a PAR-1 antagonist on human umbilical Artery Tone in vitro.
Claude A. Piantadosi - One of the best experts on this subject based on the ideXlab platform.
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bicarbonate dependent superoxide release and pulmonary Artery Tone
American Journal of Physiology-heart and Circulatory Physiology, 2003Co-Authors: Eva Nozikgrayck, Yuh-chin T. Huang, Martha Sue Carraway, Claude A. PiantadosiAbstract:Pulmonary vasoconstriction is influenced by inactivation of nitric oxide (NO) with extracellular superoxide (\batchmode \documentclass[fleqn,10pt,legalpaper]{article} \usepackage{amssymb} \usepacka...
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Vascular Signaling by Free Radicals Bicarbonate-dependent superoxide release and pulmonary Artery Tone
2003Co-Authors: Eva Nozik-grayck, Yuh-chin T. Huang, Martha Sue Carraway, Claude A. PiantadosiAbstract:Nozik-Grayck, Eva, Yuh-Chin T. Huang, Martha Sue Carraway, and Claude A. Piantadosi. Bicarbonate-dependent superoxide release and pulmonary Artery Tone. Am J Physiol Heart Circ Physiol 285: H2327–H2335, 2003. First published July 3, 2003; 10.1152/ajpheart.00507.2003.—Pulmonary vasoconstriction is influenced by inactivation of nitric oxide (NO) with extracellular superoxide (O2 ). Because the short-lived O2 anion cannot diffuse across plasma membranes, its release from vascular cells requires specialized mechanisms that have not been well delineated in the pulmonary circulation. We have shown that the bicarbonate (HCO3 )-chloride anion exchange protein (AE2) expressed in the lung also exchanges O2 for HCO3 . Thus we determined whether O2 release involved in pulmonary vascular Tone depends on extracellular HCO3 . We assessed endotheliumdependent vascular reactivity and O2 release in the presence or absence of HCO3 in pulmonary Artery (PA) rings isolated from normal rats and those exposed to hypoxia for 3 days. Lack of extracellular HCO3 in normal PA rings significantly attenuated endothelial O2 release, opposed hypoxic vasoconstriction, and enhanced acetylcholine-mediated vasodilation. Release of O2 was also inhibited by an AE2 inhibitor (SITS) and abolished in normoxia by an NO synthase inhibitor (NG-nitro-L-arginine methyl ester). In contrast, hypoxia increased PA AE2 protein expression and O2 release; the latter was not affected by NG-nitro-L-arginine methyl ester or other inhibitors of enzymatic O2 generation. Enhanced O2 release by uncoupling NO synthase with geldanamycin was attenuated by hypoxia or by HCO3 elimination. These results indicate that O2 produced by endothelial NOS in normoxia and unidentified sources in hypoxia regulate pulmonary vascular Tone via AE2.
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bicarbonate dependent superoxide release and pulmonary Artery Tone vascular signaling by free radicals
American Journal of Physiology-heart and Circulatory Physiology, 2003Co-Authors: Eva Nozikgrayck, Yuh-chin T. Huang, Martha Sue Carraway, Claude A. PiantadosiAbstract:Pulmonary vasoconstriction is influenced by inactivation of nitric oxide (NO) with extracellular superoxide (O - 2 ○). Because the short-lived O - 2 ○ anion cannot diffuse across plasma membranes, its release from vascular cells requires specialized mechanisms that have not been well delineated in the pulmonary circulation. We have shown that the bicarbonate (HCO - 3)-chloride anion exchange protein (AE2) expressed in the lung also exchanges O - 2 ○ for HCO - 3 . Thus we determined whether O - 2 ○ release involved in pulmonary vascular Tone depends on extracellular HCO - 3. We assessed endothelium-dependent vascular reactivity and O - 2 ○ release in the presence or absence of HCO - 3 in pulmonary Artery (PA) rings isolated from normal rats and those exposed to hypoxia for 3 days. Lack of extracellular HCO - 3in normal PA rings significantly attenuated endothelial O - 2 ○ release, opposed hypoxic vasoconstriction, and enhanced acetylcholine-mediated vasodilation. Release of O - 2 ○ was also inhibited by an AE2 inhibitor (SITS) and abolished in normoxia by an NO synthase inhibitor (N G -nitro-L-arginine methyl ester). In contrast, hypoxia increased PA AE2 protein expression and O - 2 ○ release; the latter was not affected by N G -nitro-L-arginine methyl ester or other inhibitors of enzymatic O - 2 ○ generation. Enhanced O - 2 ○ release by uncoupling NO synthase with geldanamycin was attenuated by hypoxia or by HCO3 elimination. These results indicate that O - 2 ○ produced by endothelial NOS in normoxia and unidentified sources in hypoxia regulate pulmonary vascular Tone via AE2.
Steffensebastian Bolz - One of the best experts on this subject based on the ideXlab platform.
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Sphingosine-1-Phosphate acutely modulates the CFTR (Cystic Fibrosis Transmembrane Regulator) transporter in an AMPK-dependent manner
The FASEB Journal, 2010Co-Authors: Firhan Atir Malik, Anja Meissner, Christine E. Bear, Steffensebastian BolzAbstract:IntroductionSphingosine-1-Phosphate (S1P) is a primary modulator of resistance Artery Tone. Its bioavailability is controlled by a rheostat between sphingosine kinase 1 and intracellular S1P phosph...
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role of sphingosine 1 phosphate phosphohydrolase 1 in the regulation of resistance Artery Tone
Circulation Research, 2008Co-Authors: Bernhard Friedrich Peter, Darcy Lidington, Aki Harada, Hanno J Bolz, Lukas Vogel, Scott P Heximer, Sarah Spiegel, Ulrich Pohl, Steffensebastian BolzAbstract:Sphingosine-1-phosphate (S1P), which mediates pleiotropic actions within the vascular system, is a prominent regulator of microvascular Tone. By virtue of its S1P-degrading function, we hypothesized that S1P-phosphohydrolase 1 (SPP1) is an important regulator of Tone in resistance arteries. Hamster gracilis muscle resistance arteries express mRNA encoding SPP1. Overexpression of SPP1 (via transfection of a SPP1wt) reduced resting Tone, Ca2+ sensitivity, and myogenic vasoconstriction, whereas reduced SPP1 expression (antisense oligonucleotides) yielded the opposite effects. Expression of a phosphatase-dead mutant of SPP1 (SPP1H208A) had no effect on any parameter tested, suggesting that catalytic activity of SPP1 is critical. The enhanced myogenic Tone that follows overexpression of S1P-generating enzyme sphingosine kinase 1 (Sk1wt) was functionally antagonized by coexpression with SPP1wt but not SPP1H208A. SPP1 modulated vasoconstriction in response to 1 to 100 nmol/L exogenous S1P, a concentration range that was characterized as S1P2-dependent, based on the effect of S1P2 inhibition by antisense oligonucleotides and 1 μmol/L JTE013. Inhibition of the cystic fibrosis transmembrane regulator (CFTR) (1) restored S1P responses that were attenuated by SPP1wt overexpression; (2) enhanced myogenic vasoconstriction; but (3) had no effect on noradrenaline responses. We conclude that SPP1 is an endogenous regulator of resistance Artery Tone that functionally antagonizes the vascular effects of both Sk1wt and S1P2 receptor activation. SPP1 accesses extracellular S1P pools in a manner dependent on a functional CFTR transport protein. Our study assigns important roles to both SPP1 and CFTR in the physiological regulation of vascular Tone, which influences both tissue perfusion and systemic blood pressure.
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sphingosine 1 phosphate modulates spiral modiolar Artery Tone a potential role in vascular based inner ear pathologies
Cardiovascular Research, 2006Co-Authors: Darcy Lidington, Ulrich Pohl, Elias Q Scherer, Elmar Oestreicher, W Arnold, Steffensebastian BolzAbstract:Objective The mechanisms regulating spiral modiolar Artery (SMA) Tone are not known, yet their characterization is pivotal for understanding inner ear blood flow regulation. Sphingosine-1-phosphate (S1P), known to stimulate vasoconstriction in several vascular beds, is a candidate regulator of SMA Tone with potential pathophysiological relevance. Methods Gerbil SMAs were isolated, cannulated and pressurized (30 mm Hg transmural) for experimentation under near-in vivo conditions. For functional experiments, vascular diameter and intracellular Ca2+ were simultaneously measured. Standard RT-PCR and immunohistochemical techniques were also employed. Results mRNA transcripts encoding sphingosine kinase, S1P phosphohydrolase and three S1P receptors (S1P1–3) were detected in the SMA. S1P induced dose-dependent vasoconstriction of the SMA (EC50=115nmol/L), and enhanced the apparent Ca2+-sensitivity of the contractile apparatus. Noradrenaline did not elicit vasoconstriction. The Rho kinase inhibitor Y27632 (1μmol/L) reversed S1P-induced vasoconstriction and the S1P-mediated enhancement of Ca2+-sensitivity. RhoA was observed to translocate to the plasma membrane in response to stimulation with 30μmol/L S1P. Conclusion We conclude that all key signalling pathway constituents are present at the mRNA level for S1P to act as an endogenous regulator of SMA Tone. S1P stimulates potent, RhoA/Rho kinase-dependent SMA vasoconstriction and Ca2+ sensitization. The high sensitivity to S1P suggests that SMA vasoconstriction is likely to occur under pathological conditions that increase intramural S1P concentrations (i.e., inflammation). From a clinical perspective, the present study identifies new potential therapeutic targets for the treatment of vascular-based, “stroke-like” inner ear pathologies: the enzymes responsible for S1P bioavailability and the S1P receptors.
Attilio Maseri - One of the best experts on this subject based on the ideXlab platform.
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epicardial coronary Artery Tone and reactivity in patients with normal coronary arteriograms and reduced coronary flow reserve syndrome x
Journal of the American College of Cardiology, 1991Co-Authors: Juan Carlos Kaski, Dimitris Tousoulis, Alfredo R Galassi, Filippo Crea, Eugene P Mcfadden, Wagner I Pereira, Attilio MaseriAbstract:The vasomotor response of proximal and distal angiographically normal coronary Artery segments was studied in 12 patients with syndrome X, 17 age- and gender-matched patients with chronic stable angina and 10 control subjects with atypical chest pain and a normal coronary arteriogram. Ergonovine (300 fig by intravenous injection) and isosorbide dinitrate (1 mg by intracoronary injection) were administered to all patients. Computerized coronary Artery diameter measurement (angiographically normal segments only) was carried out before and after the administration of ergonovine and nitrate. Baseline intraluminal diameters (mean ± SEM) of proximal and distal coronary segments were not significantly different in control subjects and patients with syndrome X or coronary Artery disease (proximal 2.88 ± 0.19,3.01 ± 0.13 and 2.86 ± 0.13 mm; distal 1.57 ± 0.09,1.70 ± 0.10 and 1.61 ± 0.06 mm, respectively). With ergonovine, proximal segments constricted by 10 ± 2%, 7 ± 2% and 11 ± 3% and distal segments by 12 ± 3%, 14 ± 3% and 14 ± 2% in control subjects and patients with syndrome X or coronary Artery disease, respectively (p = NS). With isosorbide dinitrate, proximal coronary segments dilated by 11 ± 2%, 10 ± 2% and 8 ± 2% (p = NS) and distal segments by 15 ± 2%, 11 ± 3% and 13 ± 2% (p = NS) in control subjects and patients with syndrome X or coronary Artery disease, respectively. Within groups, constriction in response to ergonovine and dilation in response to nitrate were not significantly different in proximal and distal segments. The results of this study indicate that coronary diameters and the vasomotor response to ergonovine and isosorbide dinitrate of angiographically normal coronary Artery segments at rest are not significantly different in patients with noncardiac chest pain, syndrome X or coronary Artery disease. Although coronary flow reserve is impaired in patients with syndrome X, reactivity of large epicardial vessels to nitrate and ergonovine is within the physiologic range in these patients.
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comparison of epicardial coronary Artery Tone and reactivity in prinzmetal s variant angina and chronic stable angina pectoris
Journal of the American College of Cardiology, 1991Co-Authors: Juan Carlos Kaski, Dimitris Tousoulis, Stavros Gavrielides, E Mcfadden, Alfredo R Galassi, Filippo Crea, Attilio MaseriAbstract:Abstract It has been suggested that a generalized coronary vasomotion disorder is present in variant angina and that evaluation of baseline coronary Artery Tone may be useful for predicting the occurrence of coronary Artery spasm. The vasomotor response of angiographically normal proximal and distal coronary Artery segments was studied in 9 patients with atypical chest pain and normal coronary arteriograms (control group), 13 patients with active variant angina and 41 patients with chronic stable angina. Ergonovine (intravenous, 100 to 300 μg, or intracoronary, 8 to 20 μg, was administered to all 22 patients in the control and variant angina groups and to 11 of the 41 patients with chronic stable angina. All patients also received intracoronary isosorbide dinitrate (1 to 2 mg). Computerized coronary Artery diameter measurement of angiographically normal segments was carried out before and after ergonovine and nitrate administration. Mean baseline intraluminal diameter of proximal and distal coronary segments was not significantly different in control patients and those with variant angina (nonspastic segments only) or coronary Artery disease (proximal 2.89 ± 0.15, 2.83 ± 0.14 and 2.82 ± 0.09 mm; distal 1.60 ± 0.08, 1.63 ± 0.07 and 1.62 ± 0.06 mm, respectively). After ergonovine, proximal segments constricted by 10 ± 2%, 15 ± 3% and 11 ± 4% and distal segments by 11 ± 3%, 11 ± 2% and 14 ± 3% in control, variant angina and coronary Artery disease groups, respectively (p = NS). After isosorbide dinitrate, proximal coronary segments dilated by 13 ± 2%, 11 ± 3% and 8 ± 2% (p = NS) and distal segments by 13 ± 3%, 14 ± 4% and 15 ± 2% (p = NS) in control, variant angina and coronary Artery disease groups, respectively. The results of this study indicate that rest baseline coronary Tone and the vasomotor response of angiographically normal coronary Artery segments to ergonovine and isosorbide dinitrate are similar in patients with noncardiac chest pain, Prinzmetal's variant angina and coronary Artery disease. Evaluation of basal coronary Artery diameter, therefore, is not useful for predicting the occurrence or location of coronary spasm.
Akira Takeshita - One of the best experts on this subject based on the ideXlab platform.
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Effects of N-nitro-L-arginine on coronary Artery Tone and reactive hyperemia after brief coronary occlusion in conscious dogs
Coronary Artery Disease, 1994Co-Authors: Kouhei Muramatsu, Kensuke Egashira, Kohtaro Numaguchi, Teisuke Takahashi, H. Kasuya, Akira TakeshitaAbstract:To determine the role of an endothelium-derived relaxing factor (nitric oxide) in controlling basal coronary Tone and coronary vasomotion after brief coronary occlusion (reactive hyperemia). In 10 chronically instrumented conscious dogs, we studied the diameter changes of the large epicardial coronary Artery and coronary blood flow in response to intracoronary administration of acetylcholine (0.1 and 1 microgram) and brief coronary occlusion for 5 and 20 s before and after intracoronary infusion of N-nitro-L-arginine (LNNA). Intracoronary infusion of LNNA (1, 3, and 10 mg) decreased the diameter of the large epicardial coronary Artery and coronary blood flow in a dose-dependent manner without altering arterial pressure and heart rate. LNNA (10 mg) significantly attenuated the increase in Artery diameter and coronary blood flow by acetylcholine. The ratio of Artery dilation to the blood flow response after acetylcholine was not affected by LNNA. LNNA (10 mg) significantly decreased the ratio of repayment to debt flow volume of reactive hyperemia, but did not affect the ratio of peak to resting flow; it also significantly attenuated the reactive dilation of the large epicardial coronary Artery after reactive hyperemia. The ratio of Artery dilation to repayment flow volume (micron/ml) during reactive hyperemia was attenuated significantly by LNNA. These findings suggest that endothelium-derived nitric oxide may contribute to basal coronary Tone and that reactive dilation of the large epicardial coronary Artery during reactive hyperemia was caused by flow-mediated nitric oxide release, whereas coronary Artery dilation after acetylcholine was caused largely by the direct receptor-mediated release of nitric oxide.
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correlation of basal coronary Artery Tone with constrictive response to ergonovine in patients with variant angina
Journal of the American College of Cardiology, 1993Co-Authors: Takeshi Kuga, Kensuke Egashira, Tetsuji Inou, Akira TakeshitaAbstract:Objectives. This study was conducted to examine whether basal coronary Artery Tone is elevated at the spastic site in patients with variant angina and to determine the significance of basal Artery Tone in predicting provocation of coronary Artery spasm. Background. Previous data have been conflicting on whether basal coronary Artery Tone is elevated in patients with variant angina. Methods. We assessed basal coronary Artery Tone by obtaining the percent increase in coronary Artery diameter induced by nitroglycerin in 20 patients with variant angina and 24 control subjects. We also examined the correlation between basal coronary Artery Tone and the constrictive response to ergonovine. Results. In the patients with variant angina in whom spasm was provoked by the lower doses (1 or 5 μg) of ergonovine, basal coronary Artery Tone was greater (p < 0.05) at the spastic site (54 ± 15% or 36 ± 16%, respectively) than at the nonspastic site (40 ± 25% or 25 ± 15%, respectively). Basal coronary Tone at the nonspastic site in these patients was greater (p < 0.01) than that in control subjects (15 ± 6%). In the patients with variant angina in whom spasm was provoked only by the higher doses (15 or 50 μg) of ergonovine, basal coronary Artery Tone was comparable at the spastic and nonspastic sites and was not different from that in control subjects. The diagnostic sensitivity and specificity of elevated basal coronary Artery Tone (≥40%) in predicting provocation of spasm were 26% and 98%, respectively. Conclusions. These results indicate that elevated basal coronary Artery Tone may be useful in predicting provocation of coronary spasm, but the normal level of basal coronary Artery Tone does not exclude such provocation.
