Smooth muscles from spastic coronary artery segments show hypercontractility to histamine

1990 ◽  
Vol 259 (1) ◽  
pp. H9-H13 ◽  
Author(s):  
S. Satoh ◽  
H. Tomoike ◽  
W. Mitsuoka ◽  
S. Egashira ◽  
H. Tagawa ◽  
...  

An animal model of coronary spasm was produced in Gottingen miniature pigs by a selective endothelial denudation of the coronary artery. Five months after the denudation, intracoronary bolus administration of 10 micrograms/kg histamine reduced the luminal diameter angiographically by 57 +/- 16 and 17 +/- 10% (P less than 0.01) in the previously denuded and contralateral control coronary arteries. Muscle fibers of 0.08–0.1 mm wide were prepared from circumferential bundles of the medial smooth muscle in the spastic and nonspastic coronary arteries. Upward shifts of either dose-tonic contraction relationships in Ca2(+)-containing solution or dose-monophasic contraction relationships in Ca2(+)-free solution were noted in muscle fibers taken from the spastic site compared with those from the nonspastic site with no difference between the mean effective dose values. After skinning the muscle fibers with saponin, there was no significant difference in the Ca2+ concentration-tension relationships between the two fibers. These findings suggest that an increased number of histaminergic receptors and/or augmentation of signal transduction, but not Ca2+ sensitivity of the contractile proteins in the medial smooth muscle cells, cause histamine-induced coronary hypercontraction.

1982 ◽  
Vol 60 (4) ◽  
pp. 576-587 ◽  
Author(s):  
Haruo Sugi ◽  
Suechika Suzuki ◽  
Tateo Daimon

The intracellular localization of activator Ca and its translocation during the mechanical activity were studied on vertebrate and invertebrate smooth muscles by fixing muscle fibers with a 1% OsO4 solution containing 2% potassium pyroantimonate for electron microscopic examination. When guinea-pig tacnia coli, Mytilus anterior byssal retractor muscle, and Dorabella longitudinal body wall muscle were fixed during the relaxed state, electron-opaque pyroantimonate precipitate containing Ca was localized along the inner surface of the plasma membrane and at other membranous structures in close apposition to the plasma membrane, in accordance with physiological evidence that these muscles contain intracellularly stored activator Ca. When they were fixed during the contracted state, the precipitate was distributed diffusely in the myoplasm in the form of small particles, indicating the release of activator Ca from the peripheral structures. The contraction in dog coronary artery smooth muscle appears to be associated with the inward movement of extracellular Ca. In accordance with this, the resting coronary artery muscle fibers exhibited the precipitate in the lumen of the caveolae, i.e., the bottle-shaped plasma membrane invaginations, but not at the peripheral intracellular structures, though the contracted fibers showed the diffuse distribution of the precipitate in the myoplasm. These results indicate that the pyroantimonate method is very effective in studying the translocation of activator Ca in various types of smooth muscle.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Suda ◽  
J Takahashi ◽  
K Hao ◽  
Y Kikuchi ◽  
T Shindo ◽  
...  

Abstract Background Although the importance of coronary functional abnormalities has been emerging, including epicardial coronary spasm (vasospastic angina, VSA) and coronary microvascular dysfunction (CMD), comprehensive evaluation of the abnormalities in the same population remains to be examined. Purpose We examined the significance of coronary functional abnormalities in a comprehensive manner for both epicardial and microvascular coronary arteries in patients with chest pain and unobstructive coronary artery disease (CAD) as well as their prognostic impacts. Methods and results We prospectively enrolled 187 consecutive patients with suspected angina and unobstructive coronary arteries (M/F 113/74, 63.2±12.3 [SD] yrs.). We performed acetylcholine (ACh) provocation tests for coronary spasm, followed by functional tests for coronary microvascular function, including coronary flow reserve (CFR) and index of microcirculation resistance (IMR) during hyperemic state induced by intravenous adenosine. Among the 187 patients, ACh test identified 128 patients with VSA (68%). There was no significant difference in age, sex, or prevalence of traditional coronary risk factors between the non-VSA and the VSA groups. The median IMR value was significantly higher in the VSA group than in the non-VSA group [17.5 (12.0, 25.3) vs. 14.7 (10.7, 17.8), P=0.02], whereas CFR values were comparable between the 2 groups [2.51 (1.72, 3.35) vs. 2.66 (1.85, 3.64), P=0.34]. During the median follow-up period of 893 days, major adverse cardiac events (MACE), including cardiac death, non-fatal myocardial infarction, and hospitalization due to unstable angina pectoris, occurred in 10 patients (5.3%). Multivariable analysis revealed that IMR correlated with the incidence of MACE [hazard ratio (HR) (95% confidence interval), 1.05 (1.02–1.09), P=0.002] and receiver-operating characteristics curve analysis identified IMR of 18.0 as the optimal cut-off value for the incidence of cardiac events. When we divided the patients into the following 4 groups according to the cut-off value of IMR (>18) and the presence or absence of VSA; G1, IMR <18 without VSA (n=45); G2, IMR ≥18 without VSA (n=14); G3, IMR <18 with VSA (n=67); and G4, IMR ≥18 with VSA (n=61), the Kaplan-Meier survival analysis showed a significantly worse prognosis in G4 compared with other 3 groups (HR [95% CI] 6.23 [1.21–118.46], P=0.002) (Figure 1). Importantly, intracoronary administration of fasudil, a Rho-kinase inhibitor, significantly ameliorated IMR in G4 (P<0.0001) (Figure 2A), and %changes in IMR in response to intracoronary fasudil were more evident in G4 compared with other 3 groups (P<0.0001) (Figure 2B). Conclusions These results provide the first evidence that in patients with chest pain and unobstructive CAD, epicardial coronary spasm and increased microvascular resistance are frequently coexisted with worse long-term prognosis, for which Rho-kinase activationmay be involved.


Author(s):  
Mischa Borsdorf ◽  
Markus Böl ◽  
Tobias Siebert

AbstractUniaxial tensile experiments are a standard method to determine the contractile properties of smooth muscles. Smooth muscle strips from organs of the urogenital and gastrointestinal tract contain multiple muscle layers with different muscle fiber orientations, which are frequently not separated for the experiments. During strip activation, these muscle fibers contract in deviant orientations from the force-measuring axis, affecting the biomechanical characteristics of the tissue strips. This study aimed to investigate the influence of muscle layer separation on the determination of smooth muscle properties. Smooth muscle strips, consisting of longitudinal and circumferential muscle layers (whole-muscle strips [WMS]), and smooth muscle strips, consisting of only the circumferential muscle layer (separated layer strips [SLS]), have been prepared from the fundus of the porcine stomach. Strips were mounted with muscle fibers of the circumferential layer inline with the force-measuring axis of the uniaxial testing setup. The force–length (FLR) and force–velocity relationships (FVR) were determined through a series of isometric and isotonic contractions, respectively. Muscle layer separation revealed no changes in the FLR. However, the SLS exhibited a higher maximal shortening velocity and a lower curvature factor than WMS. During WMS activation, the transversally oriented muscle fibers of the longitudinal layer shortened, resulting in a narrowing of this layer. Expecting volume constancy of muscle tissue, this narrowing leads to a lengthening of the longitudinal layer, which counteracted the shortening of the circumferential layer during isotonic contractions. Consequently, the shortening velocities of the WMS were decreased significantly. This effect was stronger at high shortening velocities.


Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2041
Author(s):  
Luiz Jardelino de Lacerda Neto ◽  
Andreza Guedes Barbosa Ramos ◽  
Renata Evaristo Rodrigues da Silva ◽  
Luís Pereira-de-Morais ◽  
Fernanda Maria Silva ◽  
...  

Purpose: Alternative methods for the use of animals in research have gained increasing importance, due to assessments evaluating the real need for their use and the development of legislation that regulates the subject. The principle of the 3R’s (replacement, reduction and refinement) has been an important reference, such that in vitro, ex vivo and cord replacement methods have achieved a prominent place in research. Methods: Therefore, due to successful results from studies developed with these methods, the present study aimed to evaluate the myorelaxant effect of the Dysphania ambrosioides essential oil (EODa) using a Sus scrofa domesticus coronary artery model, and the toxicity of both the Dysphania ambrosioides essential oil and its major constituent, α-terpinene, against Drosophila melanogaster in toxicity and negative geotaxis assays. Results: The EODa relaxed the smooth muscle of swine coronary arteries precontracted with K+ and 5-HT in assays using Sus scrofa domesticus coronary arteries. The toxicity results presented LC50 values of 1.546 mg/mL and 2.282 mg/mL for the EODa and α-terpinene, respectively, thus showing the EODa and α-terpinene presented toxicity to these dipterans, with the EODa being more toxic. Conclusions: Moreover, the results reveal the possibility of using the EODa in vascular disease studies since it promoted the relaxation of the Sus scrofa domesticus coronary smooth muscle.


2020 ◽  
pp. 1-5
Author(s):  
Stephan Gerling ◽  
Tobias Pollinger ◽  
Markus Johann Dechant ◽  
Michael Melter ◽  
Werner Krutsch ◽  
...  

Abstract Background: With the increased training loads at very early ages in European elite youth soccer, there is an interest to analyse coronary artery remodelling due to high-intensity exercise. Design and methods: Prospective echocardiographic study in 259 adolescent elite male soccer players and 48 matched controls. Results: The mean age was 12.7 ± 0.63 years in soccer players and 12.6 ± 0.7 years in controls (p > 0.05). Soccer players had significant greater indexed left ventricular mass (93 ± 13 g/m2 versus 79 ± 12 g/m2, p = 0.001). Both coronary arteries origin could be identified in every participant. In soccer players, the mean diameter of the left main coronary artery was 3.67 mm (SD ± 0.59) and 2.61 mm (SD ± 0.48) for right main coronary artery. Controls showed smaller mean luminal diameter (left main coronary artery, p = 0.01; right main coronary artery, p = 0.025). In soccer players, a total of 91% (n = 196) and in controls a total of 94% (n = 45) showed left main coronary artery z scores within the normal range: −2.0 to 2.0. In right main coronary artery, a pattern of z score values distribution was comparable (soccer players 94%, n = 202 vs. controls 84%, n = 40). A subgroup of soccer players had supernormal z score values (>2.0 to 2.5) for left main coronary artery (9%, n = 19, p = 0.01) and right main coronary artery (6%, n = 10, p = 0.025), respectively. Conclusion: Elite soccer training in early adolescence may be a stimulus strong enough to develop increased coronary arteries diameters. In soccer players, a coronary artery z score >2.0–2.5 might reflect a physiologic response induced by multiannual high-intensity training.


1990 ◽  
Vol 68 (5) ◽  
pp. 608-613 ◽  
Author(s):  
Mudumbi V. Ramagopal ◽  
S. Jamal Mustafa

Adenosine relaxes the coronary arteries of various species through A2 receptors. The aim of the present investigation was to evaluate the relaxing effects of adenosine in relation to the role of calcium in bovine coronary arteries by studying the vasodilatory effect of adenosine in normal and calcium-free medium and on calcium-45 efflux into calcium-free medium. Acetylcholine (ACh) and norepinephrine (NE) were used to induce tone in coronary artery rings. Adenosine, 5′-(N-ethylcarboxamido)adenosine (NECA), and N6-(L-phenylisopropyl)adenosine (L-PIA) produced concentration-dependent relaxations of the coronary artery rings. Both in normal and calcium-free medium, the order of potency for adenosine analogs (NECA > L-PIA > adenosine) was similar and 8-phenyltheophylline antagonized the relaxation responses to adenosine and its analogs. Removal of extracellular calcium shifted the concentration–response curves to the right in a parallel fashion, slowed the rate of relaxation, and in NE contracted rings reduced the maximum responses for adenosine and its analogs. In calcium-free medium, adenosine was without an effect on calcium-45 efflux in the presence of ACh. However, adenosine inhibited the stimulated calcium-45 efflux induced by NE. The data suggest that the vasodilatory action of adenosine in bovine coronary smooth muscle has both extracellular calcium-dependent and -independent components.Key words: adenosine receptors, calcium, coronary circulation, vascular smooth muscle, acetylcholine, norepinephrine.


1983 ◽  
Vol 245 (6) ◽  
pp. H937-H941 ◽  
Author(s):  
N. Toda

In helical strips of human epicardial coronary arteries, norepinephrine produced a concentration-related contraction; the contractions relative to those induced by 30 mM K+ were greater in the proximal portion of the arteries than in the distal portion. The amine-induced contraction was suppressed by treatment with phentolamine. Acetylcholine contracted human coronary arteries but, in contrast, relaxed the monkey coronary arteries (both freshly excised and cadaver) previously contracted with prostaglandin F2 alpha. Both the contraction and relaxation induced by acetylcholine were suppressed by atropine. Removal of the endothelium abolished the relaxation of monkey arteries but did not significantly alter the contraction of human arteries. Human coronary arteries responded to histamine with contractions, which were reversed to relaxations following treatment with chlorpheniramine. It is concluded that, as far as the portions of human coronary arteries used in the present study are concerned, the arterial contraction mediated via alpha-adrenoceptors is inversely related to the distance from the coronary artery orifice. Acetylcholine produces contractions of human coronary arteries, possibly due to activation of muscarinic receptors on smooth muscle cells. Histamine-induced contractions appear to be mediated via H1-receptors.


2001 ◽  
Vol 280 (2) ◽  
pp. C254-C264 ◽  
Author(s):  
Joseph A. Hypolite ◽  
Michael E. DiSanto ◽  
Yongmu Zheng ◽  
Shaohua Chang ◽  
Alan J. Wein ◽  
...  

Urinary bladder filling and emptying requires coordinated control of bladder body and urethral smooth muscles. Bladder dome, midbladder, base, and urethra showed significant differences in the percentage of 20-kDa myosin light chain (LC20) phosphorylation (35.45 ± 4.6, 24.7 ± 2.2, 13.6± 2.1, and 12.8 ± 2.7%, respectively) in resting muscle. Agonist-mediated force was associated with a rise in LC20 phosphorylation, but the extent of phosphorylation at all levels of force was less for urethral than for bladder body smooth muscle. RT-PCR and quantitative competitive RT-PCR analyses of total RNA from bladder body and urethral smooth muscles revealed only a slight difference in myosin heavy chain mRNA copy number per total RNA, whereas mRNA copy numbers for NH2-terminal isoforms SM-B (inserted) and SM-A (noninserted) in these muscles showed a significant difference (2.28 × 108 vs. 1.68 × 108 for SM-B and 0.12 × 108 vs. 0.42 × 108 for SM-A, respectively), which was also evident at the protein level. The ratio of COOH-terminal isoforms SM2:SM1 in the urethra was moderately but significantly lower than that in other regions of the bladder body. A high degree of LC20phosphorylation and SM-B in the bladder body may help to facilitate fast cross-bridge cycling and force generation required for rapid emptying, whereas a lower level of LC20 phosphorylation and the presence of a higher amount of SM-A in urethral smooth muscle may help to maintain the high basal tone of urethra, required for urinary continence.


2006 ◽  
Vol 91 (7) ◽  
pp. 2713-2720 ◽  
Author(s):  
Rose C. Christian ◽  
Peter Y. Liu ◽  
Sean Harrington ◽  
Ming Ruan ◽  
Virginia M. Miller ◽  
...  

Abstract Background: Controversy exists over the association of estrogen and cardiovascular disease. Estrogen receptors (ERs) α and β are expressed in the endothelial cells and vascular smooth muscle cells (VSMCs) of many arteries, but the relative importance of ERα or ERβ in mediating the vascular response to estrogens is not well defined, particularly in humans. We have shown previously that postmenopausal women receiving hormone therapy (HT) had lower mean coronary artery calcium, plaque area, and calcium-to-plaque ratio compared with untreated women. In this study, we examined coronary artery ERα and ERβ expression in pre- and postmenopausal women as a function of plaque area, calcium area, calcium-to-plaque ratio, and estrogen status. Methods: Coronary arteries were obtained at autopsy from a total of 55 women: nine premenopausal women, 13 postmenopausal women on HT and 33 untreated postmenopausal women (non-HT). Coronary calcification was quantified by contact microradiography, and atherosclerotic plaque area was measured histologically. Coronary artery cross-sections were immunostained for ERα and ERβ, and the amount of receptors was estimated semiquantitatively in each arterial wall layer (intima, adventitia, and media). Double immunofluorescence was used to colocalize ERα and ERβ with smooth muscle actin, a marker of VSMCs. Results: ERβ and ERα were expressed in all artery wall layers, but most avidly in the media (P = 0.001), and colocalized with VSMCs. ERβ expression exceeded ERα expression in all wall layers (P &lt; 0.001) and was adjacent to areas of calcium deposition. ERβ expression in the intimal layer correlated with calcium content, plaque area, and calcium-to-plaque ratio (all P &lt; 0.01) and tended to be greater in non-HT than in HT women (P = 0.06). ERα expression did not vary significantly among groups, nor did it correlate with calcium content, plaque area or calcium-to-plaque ratio. Expression of ERα but not ERβ declined with age (P &lt; 0.01) in HT women only. Age had no effect on ERα or ERβ expression in non-HT or premenopausal women. Conclusions: ERβ is the predominant ER in human coronary arteries and correlates with coronary calcification, a marker of severe atherosclerosis. Increased ERβ expression is linked to advanced atherosclerosis and calcification independent of age or hormone status. Future pharmacogenetic studies that target this receptor are needed to confirm causality.


1989 ◽  
Vol 257 (1) ◽  
pp. H330-H333 ◽  
Author(s):  
U. Hoeffner ◽  
M. Feletou ◽  
N. A. Flavahan ◽  
P. M. Vanhoutte

Experiments were designed to analyze the effects of ouabain on the response of vascular smooth muscle to endothelium-derived relaxing factors released under basal conditions and on stimulation with acetylcholine or bradykinin. Bioassay rings of canine coronary artery (without endothelium) were superfused with perfusate from canine left circumflex coronary arteries with endothelium (donor arteries). During contractions of the bioassay ring evoked by prostaglandin F2 alpha, the relaxations caused by endothelium-derived relaxing factor(s), released under basal conditions or on exposure of the endothelial cells of the donor artery to maximally effective concentrations of acetylcholine, were reduced by incubation of the bioassay ring with ouabain. However, the relaxations evoked by infusion of bradykinin were not altered by incubation of the bioassay rings with ouabain. These experiments demonstrate the release of two endothelium-derived relaxing factors that can be distinguished using ouabain.


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