JOURNAL HOME CME HOME THIS MONTH PAST ISSUES ETOC COLLECTIONS
AUTHORS REVIEWERS EDITORIAL BOARD FEEDBACK RSS HELP
A&A International Anesthesia Research Society
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mousa, W. F.
Right arrow Articles by Fukuda, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mousa, W. F.
Right arrow Articles by Fukuda, K.
Anesth Analg 2000;91:62-67
© 2000 International Anesthesia Research Society

CARDIOVASCULAR ANESTHESIA

Thiopental Induces Contraction of Rat Aortic Smooth Muscle Through Ca2+ Release from the Sarcoplasmic Reticulum

Wesam F. Mousa, MD, Taijiro Enoki, MD, and Kazuhiko Fukuda, MD

Department of Anesthesia, Kyoto University Hospital, Kyoto, Japan

Address correspondence and reprint requests to Taijiro Enoki, MD, Department of Anesthesia, Kyoto University Hospital, Kyoto 606-8507, Japan.


   Abstract
Top
 Abstract
Introduction
 Method
 Results
 Discussion
 References
 
Little is known about the mechanism of thiopental-induced contraction in vascular smooth muscle. This study aimed to clarify this question by conducting isometric tension experiments and 45Ca2+ flux measurements in endothelium-denuded rat aortic rings. Thiopental induced a concentration-dependent contraction under basal tension. This contraction was enhanced when rings were precontracted with phenylephrine in the presence of verapamil. In Ca2+-free solution, thiopental-induced contraction was reduced but not abolished with high concentrations. Ca2+ store depletion with a maximum dose of caffeine in Ca2+-free solution further reduced the contraction by subsequent thiopental. Ca2+ store depletion with thapsigargin completely abolished contraction by thiopental. 45Ca2+ influx experiment in the presence of verapamil showed that thiopental could not induce any Ca2+ influx with or without phenylephrine prestimulation. The 45Ca2+ efflux experiment showed more evidence of thiopental-induced Ca2+ release, which was abolished by thapsigargin. In conclusion, thiopental induces contraction in rat aortic smooth muscle by releasing Ca2+ from the sarcoplasmic reticulum without Ca2+ influx.

Implications: This is the first study providing evidence that thiopental-induced vascular contraction is caused by Ca2+ release from the sarcoplasmic reticulum of the smooth muscle.


   Introduction
Top
 Abstract
 Introduction
Method
 Results
 Discussion
 References
 
Barbiturates suppress contraction of isolated vessels from various tissues (1–4). However, thiamylal and thiopental can also induce vasoconstriction in isolated arteries depending on the experimental conditions (4–7). Although vasodilation by barbiturates has been explained by inhibition of voltage-operated Ca2+ channels (VOCC) (2,3) and reduced Ca2+ sensitivity of the muscle proteins (2,4), the mechanism(s) of contraction by barbiturates is little known.

There is some evidence suggesting that Ca2+ plays an important role in barbiturate-induced contraction. Kitamura et al. (4), using a Ca2+-indicator dye in rat aorta, demonstrated that the contraction induced by thiopental and thiamylal under basal tension was associated with increased free cytosolic Ca2+ concentration ([Ca2+]i), although they did not specify the source of Ca2+. Hatano et al. (7), by recording tension in various extracellular conditions, suggested that thiamylal-induced contraction was mainly caused by influx of Ca2+ from the extracellular fluid via pathways other than VOCC. However, the mechanism of [Ca2+]i increase by thiopental has not been explored.

In this study, we tried to elucidate the mechanism of contraction induced by thiopental. In particular, we sought to analyze the effect of thiopental on Ca2+ movement in smooth muscle. We prepared rat aorta of which endothelium was removed and conducted 45Ca2+ influx and efflux experiments that can trace Ca2+ movements directly, in addition to tension experiments. Our results showed that thiopental induces contraction by releasing Ca2+ from the intracellular Ca2+ stores but not by stimulating Ca2+ influx.


   Method
Top
 Abstract
 Introduction
 Method
Results
 Discussion
 References
 
This study was approved by our Animal Use Committee and conducted according to guidelines of the Japanese Pharmacological Society. Seventy-six male Wistar rats (250–350 g) were used in this study. Rats were anesthetized with diethyl ether and killed by exsanguination from a common carotid artery. The descending part of the thoracic aorta was isolated and cut into rings 2 mm wide for tension recording and 7–9 mm wide for 45Ca2+ flux measurement. The endothelium was removed by rotating the rings around a rough-surfaced needle.

The aortic rings were mounted horizontally in organ baths (37°C) filled with 5 mL of Krebs-Ringer solution aerated with a 95% O2/5% CO2 gas mixture. Isometric tension was recorded with a force displacement transducer. The rings were allowed to equilibrate for 60 min under an optimal resting tension of 2 g and then contracted with KCl 30 mM to elicit a reference value (100%) in each ring. Endothelial denudation was confirmed by the inability of 10 µM acetylcholine to cause relaxation in KCl-contracted rings. Effects of thiopental were examined under several conditions: 1) under basal condition without any pretreatment, 2) under submaximum contraction with 300 nM phenylephrine with or without previous VOCC inhibition by 10 µM verapamil, 3) after removal of extracellular Ca2+ by replacing bath solution 3 times with Ca2+-free Krebs-Ringer solution containing 1 mM EGTA, 4) after supramaximum contraction with 35 mM caffeine in Ca2+-free Krebs-Ringer solution, followed by washout of caffeine with Ca2+-free Krebs-Ringer solution, and 5) after treatment with a supramaximum concentration of 1 µM thapsigargin, an inhibitor of Ca2+ adenosine triphosphatases of the sarcoplasmic reticulum (SR) (8), followed by washout of the drug with normal Krebs-Ringer solution. When the tension became stable after each treatment, thiopental 10-5–10-3 M was added to the bath. Although thiopental 10-3 M did not appear to evoke maximal contraction in some conditions, concentrations above this were not used because they generated precipitation in the solution. A single dose of thiopental was given in one experiment, and the peak of tension increment after thiopental was measured in each ring. In the experiment with thapsigargin, thiopental was given cumulatively because thiopental did not cause contraction as described later.

For measuring unidirectional 45Ca2+ influx, we performed experiments according to a method described previously (9,10). Aortic strips were bathed in HEPES-buffered saline solution (HBSS) bubbled with air for 60 min at 37°C. Verapamil 10 µM was included in the HBSS throughout the experiment. Then the strips were transferred to 45Ca2+ (1 µCi/mL)-labeled HBSS containing either 0, 10-4, or 10-5 M thiopental. They were incubated in the labeled solution for 5 min. During such a short period, back flow of 45Ca2+ out of the cell can be considered negligible; therefore, the amount of 45Ca2+ taken into the tissue can be assumed to reflect unidirectional Ca2+ influx (9). After exposure to 45Ca2+, the strips were bathed for 50 min in an ice-cold Ca2+-free HBSS containing EGTA 2 mM to remove the extracellular 45Ca2+. The strips were then blotted, weighed, and incubated overnight in 1 mL of EDTA 5 mM solution at room temperature to extract 45Ca2+ inside the cell. Finally, 0.8 mL of the solution was transferred to Ready Cap (Beckman, Fullerton, CA) dishes, dried, and analyzed for 45Ca2+ by using a scintillation counter. Data were expressed as the estimated amount of Ca2+ influx (µmol) per kg aorta (wet weight). In some groups, strips were stimulated with phenylephrine 300 nM 10 min before the labeling. For these strips, the labeled solution also contained phenylephrine in addition to thiopental 0, 10-4, or 10-3 M.

The 45Ca2+ efflux experiment was performed to observe Ca2+ release by thiopental. Although it is an old-fashioned technique, a recent work has reevaluated this method to conclude that the 45Ca2+ efflux pattern obtained from whole vascular tissue directly reflects intracellular Ca2+ release without any interference by the cell membrane or the extracellular matrix (11). We followed a method that has been described previously (12) with some modifications. Aortic strips were prepared as described above and incubated in 45Ca2+ (3 µCi/mL)-labeled HBSS at 37°C for 2 h. At the end of the exposure to 45Ca2+, the strips were rinsed for 5 s in a large volume of HBSS to remove the adherent labeling solution. Then, the strips were bathed sequentially for 5 min in a series of wells of a 24-well tissue culture plate containing 1 mL HBSS maintained at 37°C. The strips were removed after 80 min of efflux, and the solutions in each well were analyzed for 45Ca2+ as described above. Some strips were exposed to thiopental 10-3 M from 60 to 80 min, which was included in the efflux solution. Rate of Ca2+ loss (µmol · kg-1 · min-1) was calculated at each time point to obtain the efflux pattern.

Krebs-Ringer solution had the following composition (in mM): NaCl 120, KCl 5.0, CaCl2 2.0, MgCl2 1.0, NaHCO3 25.0, and glucose 5.5; the pH of the solution was 7.3–7.4 when the solution was aerated with a 95% O2/5%CO2 gas mixture. To prepare Ca2+-free Krebs-Ringer solution, CaCl2 was replaced by 1 mM EGTA. HBSS had the following composition (in mM): NaCl 140, KCl 5.0, CaCl2 2.0, MgCl2 1.0, glucose 5.5, HEPES 10.0; pH was adjusted to 7.30–7.35 with NaOH. Sodium thiopental was dissolved in distilled water. An appropriate concentration of the thiopental solution was added to the bathing solution on a scale of 1% vol/vol. The other drugs used were phenylephrine and thapsigargin, acetylcholine, verapamil, EGTA, EDTA, and caffeine.

All data were presented as mean ± SD; n represents the number of rings examined in each group. Concentration-response relationship was statistically confirmed by using Jonckheere’s ranked sum test. Pairwise comparisons between data from the same rat were performed by using paired t-tests. Other comparisons between two groups were performed by using Student’s t-test. Comparisons among more than two groups were performed by using one-way factorial analysis of variance followed by post hoc Tukey’s test for comparison with the control. Differences at P < 0.05 were considered significant.


   Results
Top
 Abstract
 Introduction
 Method
 Results
Discussion
 References
 
Tension Experiments
Figure 1A shows typical responses to thiopental under the basal condition. Thiopental, from 3 x 10-5 M to 10-3 M, induced a contraction that was easily reversed after washout of the drug. Tension increments induced by thiopental were concentration-dependent (P < 0.01) (Fig. 2). The effect of thiopental was examined under raised tension level by using a submaximum dose of phenylephrine. Phenylephrine induced sustained contraction (94% ± 29% of KCl contraction, n = 60) which was approximately 80% of the maximum contraction by phenylephrine in our preliminary study. Subsequent contraction by thiopental was not changed or slightly depressed compared with control (Fig. 2). After pretreatment of the rings with verapamil, phenylephrine-induced contraction was suppressed (61% ± 25%, n = 60, P < 0.01), but subsequent contraction by thiopental was significantly larger than those under the basal condition (Figs. 1B and 2).



View larger version (12K):
[in this window]
[in a new window]
  		Figure 1. Typical recordings of thiopental (10-5-10-3 M)-induced contraction in rat aorta. A, Thiopental (TP) applied on basal tension. B, TP applied on verapamil-treated rings precontracted submaximally with phenylephrine (Phe). C, TP applied in Ca2+-free EGTA-containing solution.

 


View larger version (18K):
[in this window]
[in a new window]
  		Figure 2. Comparison of thiopental-induced contraction in normal solution, in phenylephrine-precontracted rings with and without verapamil and in Ca2+-free solution. Maximum tension increment after introduction of TP was expressed as percentage of KCl-induced reference contraction in each ring. Mean ± SD are shown. *P < 0.05 versus normal solution. n = 12 each group.

 
To examine the role of extracellular Ca2+ in thiopental-induced contraction, the bathing solution was replaced by Ca2+-free solution. Although resting tension was not changed from the basal level in the Ca2+-free solution, thiopental-induced contraction was markedly reduced, being evident only above 3 x 10-3 M (Figs. 1C and 2). To examine the role of intracellular Ca2+ in the contraction by thiopental, we tried to deplete intracellular Ca2+ store using a supramaximal concentration of caffeine in Ca2+-free solution. Caffeine induced a transient contraction followed by a small relaxation below the basal level (Fig. 3). After washout of caffeine and recovery of the tension to the basal level, 10-3 M thiopental was added. Thiopental-induced contraction was significantly reduced after caffeine (4% ± 2% of KCl contraction, n = 12, P < 0.05) compared with the control ring without caffeine, which was taken from the same rat and simultaneously exposed to thiopental in Ca2+-free solution (8% ± 5%, n = 12). We also used thapsigargin, another drug that depletes Ca2+ from the sarcoplasmic reticulum (9). Thapsigargin induced a slowly developing contraction (56% ± 24% of KCl contraction, n = 8) that was resistant to extensive washes (Fig. 4), which could be explained by the irreversible inhibition of Ca2+ adenosine triphosphatases of the SR (8,13). More than 2 h were necessary for the contraction to become stable. Cumulative doses of thiopental 10-5, 10-4, and 10-3 M could not induce contraction in any ring examined (n = 4) (Fig. 4). The other four rings were treated with verapamil 10 µM and phenylephrine 300 nM by expecting their augmenting effect on contraction, which further increased the tension level by 70% ± 19% of KCl contraction. Again, thiopental 10-5, 10-4, and 10-3 M failed to evoke any contraction in all rings examined (Fig. 4). With or without phenylephrine, thiopental 10-3 M induced a profound relaxation rather than contraction in each ring (Fig. 4).



View larger version (11K):
[in this window]
[in a new window]
  		Figure 3. Typical recordings of thiopental (TP) 10-3 M-induced contraction with and without pretreatment with 35 mM caffeine (Caf) in Ca2+-free solution. Recordings were made simultaneously in two rings from the same rat. Caffeine pretreatment significantly reduced thiopental-induced contraction.

 


View larger version (13K):
[in this window]
[in a new window]
  		Figure 4. Typical recordings of the effect of thapsigargin (TG) 1 µM pretreatment on thiopental (TP)-induced contraction. As the action of thapsigargin is irreversible, rings were washed with normal solution several times until contraction became stable. Thiopental was added in incremental doses (10-5, 10-4, and 10-3 M). In the lower panel, rings were treated with verapamil (Ver) and phenylephrine (Phe) before adding thiopental. Thiopental never induced contraction with or without phenylephrine. Interruption in the lower panel represents a slowly developing contraction for 40 min.

 
45Ca2+ Influx Experiment
In the normal solution, thiopental 10-4 or 10-3 M did not yield a statistical difference in Ca2+ influx compared with the control (n = 12 in each group) (Fig. 5). Stimulation of the rings with phenylephrine 10 min before labeling significantly increased Ca2+ influx compared with the control (Fig. 5). As this Ca2+ influx occurred in the presence of verapamil, it should reflect the activity of Ca2+ channels other than VOCC stimulated by phenylephrine (10). Although this condition augmented thiopental-induced contraction in tension experiments, Ca2+ influx was never enhanced by 10-4 or 10-3 M thiopental (Fig. 5). There was a tendency that 10-3 M thiopental rather reduced Ca2+ influx, although no statistical difference was detected among groups.



View larger version (16K):
[in this window]
[in a new window]
  		Figure 5. Modulation of Ca2+ influx by thiopental in the presence of verapamil 10 µM with or without phenylephrine 300 nM. Thiopental did not change Ca2+ influx either with or without phenylephrine (n = 10 each). Note that for 0 and 10-4 M thiopental, but not for 10-3 M, stimulation of the strips with phenylephrine significantly enhanced the Ca2+ influx compared with the basal conditions. *P < 0.05 compared without phenylephrine.

 
45Ca2+ Efflux Experiment
Figure 6A shows the 45Ca2+ efflux pattern without any drug in the bathing solution. The spontaneous efflux should represent the release of both extracellularly bound 45Ca2+ and stored 45Ca2+ in the SR; however, the proportion of the former becomes smaller with time because of faster washout from this compartment (11). Thiopental 10-3 M, added after 60 min to the efflux solution, transiently accelerated Ca2+ efflux (Fig. 6B). During the first 5 min after thiopental, Ca2+ efflux was significantly increased compared with that during the last 5 min before thiopental (P < 0.05, n = 5). When thapsigargin 1 µM was included in the efflux solutions from the beginning of wash, thiopental-induced Ca2+ efflux was abolished (Fig. 6B).



View larger version (18K):
[in this window]
[in a new window]
  		Figure 6. Ca2+ efflux curves. Mean ± SD are shown. A, Spontaneous efflux without any drugs in the bathing solution. Time represents the duration of wash. n = 5 at each point. B, Strips were exposed to thiopental 10-3 M (TP) at 60 min and thereafter in normal solution or in solution containing 1 µM thapsigargin. n = 5 at each point. *P < 0.05 compared with the efflux just before thiopental.

 

   Discussion
Top
 Abstract
 Introduction
 Method
 Results
 Discussion
References
 
In this study, thiopental induced concentration-dependent contraction in endothelium-denuded rat aortic smooth muscle. The result is consistent with previous studies in various vascular tissues (4–7). Additional tension and 45Ca2+ flux experiments were conducted to examine the role of Ca2+ influx and release in thiopental-induced contraction.

The contractile effect of thiopental was markedly reduced in Ca2+-free solution, which may suggest a possible role of Ca2+ influx. However, the 45Ca2+ influx experiment, a more immediate and reliable method to trace Ca2+ movement (9), disproved Ca2+ influx by thiopental either with or without phenylephrine prestimulation. Therefore, suppression of contraction should be ascribed to the exposure of the rings to Ca2+-free solution per se, which might have reduced intracellular Ca2+ content of the smooth muscle cells.

However, the possibility of Ca2+ release by thiopental, as suggested from the contraction in Ca2+-free solution, was tested in additional tension experiments. Ca2+ store depletion by caffeine reduced the second contraction by thiopental, suggesting that thiopental-induced contraction is partly, but not fully, mediated by Ca2+ release from the intracellular store sensitive to caffeine. Because smooth muscle cells may have caffeine-insensitive Ca2+ stores (14) thapsigargin was used to deplete the SR completely, which abolished thiopental-induced contraction. Although increased resting tension after thapsigargin may have some influence on the effect of thiopental as with that after phenylephrine, it does not appear probable that this alone caused complete abolishment of contraction. Therefore it should be ascribed to depletion of the SR by thapsigargin. These tension experiments collectively suggest that thiopental releases Ca2+ from both the caffeine-sensitive and -insensitive parts of the SR. This hypothesis was fully supported in the 45Ca2+ efflux experiment. To our knowledge, the current study is the first that demonstrates the stimulating effect of thiopental on Ca2+ release in vascular smooth muscle.

In cardiac muscle, thiopental inhibited Ca2+ release induced by ryanodine (15) and uptake of Ca2+ by the SR (16) but did not alter Ca2+ content of the SR (16). These different responses of the SR between vascular smooth muscle and cardiac muscle may not be unacceptable, considering the differences in structure and physiological function of the SR between them. It may be interesting to examine the effect of thiopental on Ca2+ store in other cell types.

In the literature (1–4), thiopental has been shown to have vasodilating effects as well, which are evident after precontraction with high K + solution or {alpha}-agonists. In this study, vasodilation sometimes followed the transient contraction by thiopental when the resting tension was increased by phenylephrine. Pretreatment with verapamil in addition to phenylephrine increased thiopental-induced contraction. Although the resting tension before thiopental is different with and without verapamil and simple comparison may not be adequate, it appears possible that preliminary VOCC blockade masked the VOCC-blocking effect of thiopental (17), resulting in an augmentation of the contractile effect of thiopental. Even after use of verapamil, a high concentration of thiopental can cause vasodilation (Fig. 1B), whereas 45Ca2+ influx is not affected. This may possibly be explained by reduced Ca2+ sensitivity of the muscle proteins by thiopental (2,4).

This is a basic study concerned with the contractile effect of thiopental in vascular smooth muscle. Endothelium-denuded rat aorta was used to examine the direct effect of thiopental on smooth muscle. It is possible that with intact endothelium, vascular response to thiopental is different. Previous studies suggest that thiopental may suppress release of endothelium-derived relaxing factors from the endothelium (18,19), which should modify direct contractile effects of thiopental on smooth muscle. While vasoconstriction by thiopental seems to be a ubiquitous phenomenon throughout different animal species and types of vascular tissue (4–7), we cannot assert from this study that the mechanism of contraction is the same among them. Future study should be done to determine whether Ca2+ release is responsible for in vivo vascular response to thiopental in humans.

In summary, this study shows that thiopental-induced contraction of rat aorta is mediated through Ca2+ release from the SR. This is a novel finding that calls for further studies to investigate the intracellular mechanism of Ca2+ release and the clinical significance of this effect.


   Acknowledgments
 
The authors thank Kazuko Imai and Yasukuni Yamamoto of the Kyoto University Experimental Animal Institute for their help in preparing the animals.


   Footnotes
 
The work was financially supported by Grant-in-Aid for Encouragement of Young Scientists from the Ministry of Education, Science, Sports and Culture, Japan (No. 11770847).


   References
Top
 Abstract
 Introduction
 Method
 Results
 Discussion
 References
 

  1. Altura BT, Altura BM. Barbiturates and aortic and venous smooth-muscle function. Anesthesiology 1975;43:432–44.[Medline]
  2. Moriyama S, Nakamura K, Hatano Y, et al. Responses to barbiturates of isolated dog cerebral and mesenteric arteries contracted with KCl and prostaglandin F2{alpha}. Acta Anaesthesiol Scand 1990;34:523–9.[Web of Science][Medline]
  3. Yakushiji T, Nakamura K, Hatano Y, Mori K. Comparison of the vasodilator effects of thiopentone and pentobarbitone. Can J Anaesth 1992;39:604–9.[Web of Science][Medline]
  4. Kitamura R, Kakuyama M, Nakamura K, et al. Thiobarbiturates suppress depolarization-induced contraction of vascular smooth muscle without suppression of calcium influx. Br J Anaesth 1996;77:503–7.[Abstract/Free Full Text]
  5. Andreasen F, Christensen JH. Thiopentone-induced changes in the contraction pattern of vascular smooth muscle: the influence of albumin. Br J Pharmacol 1984;82:643–50.[Web of Science][Medline]
  6. Fukuda S, Inomata I, Tsuji T, Takeshita H. Thiopental potentiation of isolated rabbit pulmonary artery contractions with alpha receptor agonists. Anesthesiology 1984;60:187–92.[Medline]
  7. Hatano Y, Nakamura K, Moriyama S, et al. The contractile responses of isolated dog cerebral and extracerebral arteries to oxybarbiturates and thiobarbiturates. Anesthesiology 1989;71:80–6.[Web of Science][Medline]
  8. Pozzan T, Rizzuto R, Volpe P, Meldolesi J. Molecular and cellular physiology of intracellular calcium stores. Physiol Rev 1994;74:595–636.[Free Full Text]
  9. Meisheri KD, Hwang O, van Breemen C. Evidence for two separate Ca2+ pathways in smooth muscle plasmalemma. J Membr Biol 1981;59:19–25.[Web of Science][Medline]
  10. Hirata S, Enoki T, Kitamura R, et al. Effects of isoflurane on receptor-operated Ca2+ channels in rat aortic smooth muscle. Br J Anaesth 1998;81:578–83.[Abstract/Free Full Text]
  11. Lapidot SA, Huang BK, Fayazi A, et al. Mechanisms for Ca signaling in vascular smooth muscle: resolved from 45Ca uptake and efflux experiments. Cell Calcium 1996;19:167–84.[Medline]
  12. Deth R, Casteels R. A study of releasable Ca fractions in smooth muscle cells of the rabbit aorta. J Gen Physiol 1977;69:401–16.[Abstract/Free Full Text]
  13. Low AM, Darby PJ, Kwan C, Daniel EE. Effects of thapsigargin and ryanodine on vascular contractility: cross-talk between sarcoplasmic reticulum and plasmalemma. Eur J Pharmacol 1993;230:53–62.[Web of Science][Medline]
  14. Iino M, Kobayashi T, Endo M. Use of ryanodine for functional removal of the calcium store in smooth muscle cells of the guinea-pig. Biochem Biophys Res Comm 1988;152:417–22.[Web of Science][Medline]
  15. Komai H, Rusy BF. Effect of thiopental on Ca2+ release from sarcoplasmic reticulum in intact myocardium. Anesthesiology 1994;81:946–52.[Web of Science][Medline]
  16. Kanaya N, Zakhary DR, Murray PA, Damron DS. Thiopental alters contraction, intracellular Ca2+, and pH in rat ventricular myocytes. Anesthesiology 1998;89:202–14.[Web of Science][Medline]
  17. Yamakage M, Hirshman CA, Croxton TL. Inhibitory effects of thiopental, ketamine, and propofol on voltage-dependent Ca2+ channels in porcine tracheal smooth muscle cells. Anesthesiology 1995;83:1274–82.[Web of Science][Medline]
  18. Terasako K, Nakamura K, Toda H, et al. Barbiturates inhibit endothelium-dependent and independent relaxations mediated by cyclic GMP. Anesth Analg 1994;78:823–30.[Abstract/Free Full Text]
  19. Ishida K, Kinoshita H, Kobayashi S, Sakabe T. Thiopentone inhibits endothelium-dependent relaxations of rat aortas regulated by endothelial Ca2+-dependent K + channels. Eur J Pharmacol 1999;371:179–85.[Web of Science][Medline]
Accepted for publication April 13, 2000.




This article has been cited by other articles:


Home page
 Br J AnaesthHome page
Z. L. Brookes, C. S. Reilly, and N. J. Brown
Differential effects of propofol, ketamine, and thiopental anaesthesia on the skeletal muscle microcirculation of normotensive and hypertensive rats in vivo
Br. J. Anaesth., August 1, 2004; 93(2): 249 - 256.
[Abstract] [Full Text] [PDF]

Home page
 SEMIN CARDIOTHORAC VASC ANESTHHome page
T. A. Stekiel, Z. J. Bosnjak, and W. J. Stekiel
Effects of General Anesthetics on Regulation of the Peripheral Vasculature
Seminars in Cardiothoracic and Vascular Anesthesia, September 1, 2003; 7(3): 311 - 331.
[Abstract] [PDF]

Home page
 Br J AnaesthHome page
S. Kabara, K. Hirota, H. Yoshioka, T. Kudo, H. Ishihara, and A. Matsuki
Differential effects of thiopental on methacholine- and serotonin-induced bronchoconstriction in dogs{dagger}
Br. J. Anaesth., September 1, 2003; 91(3): 379 - 384.
[Abstract] [Full Text] [PDF]

Home page
 JNMHome page
L. M. Riou, C. Ghezzi, G. Vanzetto, A. Broisat, J.-P. Mathieu, R. Bontron, R. Pasqualini, and D. Fagret
Verapamil Does Not Inhibit 99mTcN-NOET Uptake In Situ in Normal or Ischemic Canine Myocardium
J. Nucl. Med., June 1, 2003; 44(6): 981 - 987.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Mousa, W. F.
Right arrow Articles by Fukuda, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mousa, W. F.
Right arrow Articles by Fukuda, K.

Lippincott, Williams & Wilkins Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins and Stanford University Libraries' HighWire Press®. Copyright 2000 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999 HighWire Press