Extracellular calcium-dependent and -independent effects of adenosine in bovine coronary artery

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.

1975 ◽  
Vol 229 (2) ◽  
pp. 265-269 ◽  
Author(s):  
CL Seidel ◽  
RL Schnarr ◽  
HV Sparks

The purpose of this study was to test the hypothesis that the mechanical response of coronary smooth muscle following adrenergic receptor stimulation was mediated by changes in cyclic AMP content. Dibutyryl cyclic AMP caused relaxation of coronary artery strips. Aminophyline caused relaxation and a 254% elevation of cyclic AMP content (P less than 0.005). Phenylephrine caused contraction but no significant change in cyclic AMP content (P greater than 0.4). Epinephrine alone caused contraction and a 99% elevation of cyclic AMP content (P less than 0.001). The alpha blocker, phentolamine, reversed the mechanicaal response to epinephrine, but it did not significantly (P greater than 0.15) reduce the effect of epinephrine on cyclic AMP content. Propranolol enhanced the contractile response to epinephrine and attenuated the epinephrine-induced increase in cyclic AMP content. These results suggest that the contraction of coronary arteries associated with alpha-receptor stimulation is not mediated by changes in cyclic AMP content; however, relaxation associated with beta-receptor stimulation may be mediated by an increase in cyclic AMP content.


2012 ◽  
Vol 303 (5) ◽  
pp. R513-R519 ◽  
Author(s):  
Robert D. Roghair ◽  
Kenneth A. Volk ◽  
Fred S. Lamb ◽  
Jeffrey L. Segar

Intrauterine growth restriction is associated with increased fetal glucocorticoid exposure and an increased risk of adult coronary artery disease. Coronary arteries from sheep exposed to early gestation dexamethasone (Dex) have increased constriction to angiotensin II (ANG II). Prostaglandin E2 (PGE2) helps maintain coronary dilation, but PGE2 production is acutely decreased by Dex administration. We hypothesized early gestation Dex exposure impairs adult coronary PGE2 production with subsequent increases in coronary reactivity. Dex was administered to ewes at 27–28 days gestation (term 145 days). Coronary reactivity was assessed by wire myography in offspring at 4 mo of age ( N = 5 to 7). Coronary smooth muscle cells were cultured and prostaglandin production was measured after 90 min incubation with radiolabeled arachidonate. Coronary myocytes from Dex-exposed lambs had a significant decrease in PGE2 production that was reversed with ANG II incubation. Dex-exposed coronary arteries had increased constriction to ANG II and attenuated dilatation to arachidonic acid, with the greatest difference seen after the endothelium was inactivated by rubbing. Preincubation with the cyclooxygenase (COX) inhibitor indomethacin altered control responses and recapitulated the heightened coronary tone seen following Dex exposure. We conclude that impaired coronary smooth muscle COX-mediated PGE2 production contributes to the coronary dysfunction elicited by early gestation Dex. Programmed inhibition of vasodilatory prostanoid production may link an adverse intrauterine environment with adult coronary artery disease.


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.


2011 ◽  
Vol 89 (7) ◽  
pp. 467-476 ◽  
Author(s):  
Ji Seok Baik ◽  
Ju-Tae Sohn ◽  
Seong-Ho Ok ◽  
Jae-Gak Kim ◽  
Hui-Jin Sung ◽  
...  

Levobupivacaine is a long-acting local anesthetic that intrinsically produces vasoconstriction in isolated vessels. The goals of this study were to investigate the calcium-dependent mechanism underlying levobupivacaine-induced contraction of isolated rat aorta in vitro and to elucidate the pathway responsible for the endothelium-dependent attenuation of levobupivacaine-induced contraction. Isolated rat aortic rings were suspended to record isometric tension. Cumulative levobupivacaine concentration–response curves were generated in either the presence or absence of the antagonists verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, Gd3+, NW-nitro-l-arginine methyl ester (L-NAME), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), and methylene blue, either alone or in combination. Verapamil, nifedipine, SKF-96365, 2-aminoethoxydiphenylborate, low calcium concentrations, and calcium-free Krebs solution attenuated levobupivacaine-induced contraction. Gd3+ had no effect on levobupivacaine-induced contraction. Levobupivacaine increased intracellular calcium levels in vascular smooth muscle cells. L-NAME, ODQ, and methylene blue increased levobupivacaine-induced contraction in endothelium-intact aorta. SKF-96365 attenuated calcium-induced contraction in a previously calcium-free isotonic depolarizing solution containing 100 mmol/L KCl. Levobupivacaine-induced contraction of rat aortic smooth muscle is mediated primarily by calcium influx from the extracellular space mainly via voltage-operated calcium channels and, in part, by inositol 1,4,5-trisphosphate receptor-mediated release of calcium from the sarcoplasmic reticulum. The nitric oxide – cyclic guanosine monophosphate pathway is involved in the endothelium-dependent attenuation of levobupivacaine-induced contraction.


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.


2014 ◽  
Vol 307 (2) ◽  
pp. H134-H142 ◽  
Author(s):  
Praveen Shukla ◽  
Srinivas Ghatta ◽  
Nidhi Dubey ◽  
Caleb O. Lemley ◽  
Mary Lynn Johnson ◽  
...  

The mechanisms underlying developmental programming are poorly understood but may be associated with adaptations by the fetus in response to changes in the maternal environment during pregnancy. We hypothesized that maternal nutrient restriction during pregnancy alters vasodilator responses in fetal coronary arteries. Pregnant ewes were fed a control [100% U.S. National Research Council (NRC)] or nutrient-restricted (60% NRC) diet from days 50 to 130 of gestation (term = 145 days); fetal tissues were collected at day 130. In coronary arteries isolated from control fetal lambs, relaxation to bradykinin was unaffected by nitro-l-arginine (NLA). Iberiotoxin or contraction with KCl abolished the NLA-resistant response to bradykinin. In fetal coronary arteries from nutrient-restricted ewes, relaxation to bradykinin was fully suppressed by NLA. Large-conductance, calcium-activated potassium channel (BKCa) currents did not differ in coronary smooth muscle cells from control and nutrient-restricted animals. The BKCa openers, BMS 191011 and NS1619, and 14,15-epoxyeicosatrienoic acid [a putative endothelium-derived hyperpolarizing factor (EDHF)] each caused fetal coronary artery relaxation and BKCa current activation that was unaffected by maternal nutrient restriction. Expression of BKCa-channel subunits did not differ in fetal coronary arteries from control or undernourished ewes. The results indicate that maternal undernutrition during pregnancy results in loss of the EDHF-like pathway in fetal coronary arteries in response to bradykinin, an effect that cannot be explained by a decreased number or activity of BKCa channels or by decreased sensitivity to mediators that activate BKCa channels in vascular smooth muscle cells. Under these conditions, bradykinin-induced relaxation is completely dependent on nitric oxide, which may represent an adaptive response to compensate for the absence of the EDHF-like pathway.


2021 ◽  
Vol 27 (4) ◽  
pp. 41-46
Author(s):  
U.Ye. Pidvalna ◽  
D.M. Beshley ◽  
M.Z. Mirchuk ◽  
L.R. Mateshuk-Vatseba

Morphometric analysis of the structures of the aortic bulb and coronary arteries is necessary for the planning of cardiac surgery and endovascular interventions. The aim of the study was to determine the height of the coronary arteries branching in healthy women of Lviv city and Lviv region and to determine the relationship between the height of the location of the orifice of the coronary artery with anthropometric indicators. Fifteen computed tomography images with contrast of female thorax without heart and ascending aortic lesions (normal) were selected for the study. The height of the upper and lower edges of the coronary arteries was measured; height of Valsalva sinuses. The comparison of the mean values was performed according to the Student’s t-test. The correlation between the observed variables (age, height, body weight, body mass index, body surface area, height of the sinuses of Valsalva) was calculated using the Pearson linear correlation method (r). According to the study, the population group consisted of persons of the second period of adulthood (46.67 %) and the elderly (53.33 %). According to the body mass index, 80 % were overweight or obese I-II degree. The mean height of the coronary artery orifice in women without structural changes of the heart and ascending aorta was: 11.19±1.96 mm for the left and 11.68±1.80 mm for the right. The height of the orifice of the right and left coronary arteries were almost the same, without statistical significance (p=0.26). Analysis of the correlation between the values of the height of the orifice of the coronary artery did not show a probable dependence on height, weight, age, body mass index and body surface area. There is a direct relationship between the parameters of the height of the lower edge of the right coronary artery and the height of the upper edge of the right coronary artery (r=+0.75, p=0.001) and between the value of the lower edge of the left coronary artery and the upper edge of the left coronary artery (r=+0.63, p=0.01). Thus, the analysis of the correlation between the values of the height of the orifice of the coronary artery in women in norm and anthropometric indicators did not show a significant relationship. There was no statistical significance between the indicators of the height of the orifice of the right and left coronary arteries in women.


2021 ◽  
pp. 20-22
Author(s):  
Sony Jhansi Priya ◽  
Sangeetha A ◽  
M. Sai Krishna

Coronary artery variations are one of the commonest variations observed during clinical procedures. Normally, there are two main coronary arteries, the right coronary artery (RCA), left coronary artery (LCA).Left coronary artery gives two important branches left circumex artery (LCX) and left anterior descending (LAD) arteries. Knowledge about the coronary vessels and its variations are essential to clinicians to prevent untoward injury of vessels during any procedures. To study the morphology and variations of coronar Aim: y arteries by dissection. Materials and Methods: The present study was a cadaveric study which was conducted on 50 hearts obtained from adult human cadavers. Coronary arteries were dissected to see the origin, course and variations. The data was entered in Microsoft excel sheet and expressed in percentage. The Right Results: coronary artery branched out from the right aortic sinus and had an average diameter of 3.5mm. The left coronary artery arouse from left aortic sinus and had an average diameter of 4mm. LMCA divided into two branches in 60 percent, three branches in 30 percent and four branches in 06 percent of the hearts and direct branches from left aortic sinuus in 4 percent hearts.Based on the origin of Posterior descending or interventricular artery, Right dominance was observed in 68 percent, left dominance in 26 percent, and equal dominance in 06 percent of the hearts. Conclusion: Knowledge about the variations of coronary vessels is a prerequisite for clinicians to perform interventions of coronary vessels.


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.


1994 ◽  
Vol 267 (2) ◽  
pp. L106-L112 ◽  
Author(s):  
T. L. Croxton ◽  
C. Fleming ◽  
C. A. Hirshman

Voltage-dependent and receptor-operated Ca2+ entry mechanisms have been demonstrated in airway smooth muscle, but their relative importance for maintenance of contraction is unknown. Blockade of voltage-dependent Ca2+ channels (VDC) has produced inconsistent relaxation. We postulated regional variations in Ca2+ handling by airway smooth muscle cells and compared the efficacy of dihydropyridine VDC blockers in tracheas and bronchi. Porcine tracheal smooth muscle strips and bronchial rings were mounted in tissue baths filled with physiological solutions and isometric tension was measured. Tissues were precontracted with carbachol or KCl, and relaxation dose-response curves to nifedipine, Mn2+, or Cd2+ were obtained. Relaxation responses to nifedipine were significantly different in carbachol-contracted tracheas and bronchi. Whereas carbachol-contracted tracheal muscle completely relaxed with 10(-6) M nifedipine, bronchial smooth muscle relaxed < 50%. In contrast, KCl-contracted bronchial muscle was completely relaxed by nifedipine. The nonspecific Ca2+ channel blockers Mn2+ and Cd2+ produced similar relaxation responses in each tissue. Thus VDC are the predominant mechanism for Ca2+ entry in porcine tracheal smooth muscle, but a dihydropyridine-insensitive pathway is functionally important in carbachol-contracted porcine bronchi. Regional variation may account for apparent inconsistencies between previous studies.


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