Skip to main content
SpringerLink
Log in

An analysis of the effects of urethane on cardiovascular responsiveness to catecholamines in terms of its interference with Ca++ mobilization from both intra and extracellular pools

  • Full Papers
  • Published:
Experientia Aims and scope Submit manuscript

Summary

Urethane (1×10−2−1×10−1 M) reduced, in a concentration-dependent manner, both intra and extracellular Ca++ dependent noradrenaline-induced contractions of perfused rabbit ear artery as well as the tonic contractions produced by perfusion with high K+ solution. However, a quantitative analysis of the data indicated that for urethane concentrations similar to those found in plasma during anesthesia urethane antagonism is confined to noradrenaline-induced contractions which depend upon the mobilization of Ca++ from intracellular storage sites. In KCl-contracted arteries, urethane enhanced the relaxant effects of isoprenaline.—Urethane reduced the amplitude of contractions of spontaneously beating guinea-pig right atrium at concentrations which have only a limited effect on frequency. In addition, it decreased in a concentration-dependent manner the amplitude of isoprenaline-activated electrically driven, and K+ depolarized guinea-pig right ventricular strips. Urethane had no effect on the chrono and inotropic actions of isoprenaline on cardiac preparations. In in vivo experiments the chronotropic response to low doses of isoprenaline was significantly higher in urethane-treated as compared to unanesthetized rats. The higher dose of isoprenaline tested produced a significant fall in systolic blood pressure in urethane-anesthetized rats. A significant correlation exists between the chronotropic response to isoprenaline and resting heart rate values in urethane-anesthetized rats. These results indicate that urethane, at concentrations similar to those found in plasma during anesthesia selectively interferes with mobilization of Ca++ from intracellular storage sites. In addition, the interference of urethane anesthesia with the isoprenaline chronotropic effect ‘in vivo’ cannot be explained by a direct interference of urethane with β-adrenoceptors at cardiac level.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Altura, B. M., and Weinberg, J., Urethane and contraction of vascular smooth muscle. Br. J. Pharmac.67 (1979) 255–263.

    Article  CAS  Google Scholar 

  2. Altura, B. M., Altura, B. T., Carella, A., Turlapaty, P. D. M. V., and Weinberg, J., Vascular smooth muscle and general anesthetics. Fedn Proc.39 (1980) 1584–1591.

    CAS  Google Scholar 

  3. Armstrong, J. M., Urethane attenuates pressor responses produced by α-adrenoceptor agonists and some other vasoconstrictor agents in pithed rats. Br. J. Pharmac.74 (1981) 826P-827P.

    Google Scholar 

  4. Armstrong, J. M., Lefèvre-Borg, F., Scatton, B., and Cavero, I., Urethane inhibits cardiovascular responses mediated by the stimulation of α2-adrenoceptors in the rat. J. Pharmac. exp. Ther.223 (1982) 524–535.

    CAS  Google Scholar 

  5. Barrett, A. M., The effect of some autonomic blocking agents on the heart rates of anesthetized and pithed rats. Eur. J. Pharmac.15 (1971) 267–273.

    Article  CAS  Google Scholar 

  6. Bayley, H. S., and Christian, J. E., The distribution of N15 in rat tissues following the intraperitoneal administration of nitrogen-labeled urethane. J. Am. pharm. Ass.41 (1952) 517–521.

    Article  Google Scholar 

  7. Beickert, A., Tierexperimentelle Untersuchungen über das Schicksal des Urethan in Organismus. Z. ges. exp. Med.117 (1951) 10–16.

    Article  CAS  PubMed  Google Scholar 

  8. Bolton, T. B., Mechanism of action of transmitter and other substances on smooth muscle. Physiol. Rev.59 (1979) 606–718.

    Article  CAS  PubMed  Google Scholar 

  9. Boyland, E., and Rhoden, e., The distribution of urethane in animal tissues, as determined by a microdiffusion method, and the effects of urethane treatment on enzymes. Biochem. J.44 (1949) 528–531.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Brezenoff, H. E., Cardiovascular responses to noradrenaline in the rat before and after administration of various anesthetics. Br. J. Pharmac.49 (1973) 565–572.

    Article  CAS  Google Scholar 

  11. Buñag, R., and Mullenix, P., Augmentation of drug-induced blood pressure increases in rats by amobarbital. Br. J. Pharmac.49 (1972) 565–572.

    Google Scholar 

  12. Buñag, R. D., Propranolol in DOCA hypertensive rats. Development of hypertension inhibited and pressor responsiveness enhanced. Eur. J. Pharmac.43 (1977) 323–331.

    Article  Google Scholar 

  13. De Jonge, A., Santing, P. N., Timmermans, P. B. M. W. M., and Van Zwieten, P. A., Functional role of cardiac presynaptic α2-adrenoceptors in the bradycardia of α-adrenoceptor agonist in pentobarbitone- and urethane-anesthetized normotensive rats. J. auton. Pharm.2 (1982) 87–96.

    Article  Google Scholar 

  14. Findell, P. R., Larsen, B. R., Benson, B., and Blask, D. E., Mechanism of the effect of urethane on the secretion of prolactin in the male rat. Life Sci.29 (1981) 1515–1522.

    Article  CAS  PubMed  Google Scholar 

  15. Hamon, G., and Worcel, M., Mechanism of action of angiotensin II on excitation contraction coupling in the rat portal vein. Br. J. Pharmac.75 (1982) 425–432.

    Article  CAS  Google Scholar 

  16. Hillebrand, A., Van Der Meer, C., Ariëns, A. T., and Wijnans, M., The effect of anesthetic on the occurrence of kidney lesions caused by hypotension Eur. J. Pharmac.14 (1971) 217–237.

    Article  CAS  Google Scholar 

  17. Johansson, B., Permeability characteristics of vascular smooth muscle cells as revealed by their osmotic responses to nonelectrolytes. Acta physiol. scand.77 (1969) 282–297.

    Article  CAS  PubMed  Google Scholar 

  18. Johansson, B., and Somlyo, A. P., Electrophysiology and excitation contraction coupling, in: Handbook of Physiology. The Cardiovascular System, vol. II, pp. 301–323. Eds D. F. Bohr, A. P. Somlyo and H. V. Sparks, Jr. Am. Physiol. Soc., Bethesda, MD 1980.

    Google Scholar 

  19. Kauffmann, R., Bayer, R., Fürniss, T., Krause, N., and Tritthart, H., Calcium movement controlling cardiac contractility II. Analog computation of cardiac excitation-contraction coupling on the basis of calcium kinetics in a multi-compartment model. J. molec. cell. Cardiol.6 (1974) 543–559.

    Article  Google Scholar 

  20. Leenen, F. H. H., and Provoost, A. P., Maintenance of blood pressure by β-adrenoceptor mediated renin release during different forms of anesthesia in rats. Can. J. Physiol. Pharmac.59 (1981) 364–370.

    Article  CAS  Google Scholar 

  21. Litchfield, J. T., and Wilcoxon, F., A simplified method of evaluating dose effect response J. Pharmac. exp. Ther.96 (1949) 99–113.

    CAS  Google Scholar 

  22. Maggi, C. A., and Meli, A., Inhibition of adrenaline induced compensatory vagal discharge in the rat as an in vivo tool for predicting the mechanism of action of antispasmodics. J. pharmac. Meth.5 (1981) 347–352.

    Article  CAS  Google Scholar 

  23. Maggi, C. A., and Meli, A., Unsuitability of urethane anesthetized rats for testing potential β-adrenoreceptors blockers. Experientia38 (1982) 517–518.

    Article  CAS  PubMed  Google Scholar 

  24. Maggi, C. A., Santicioli, P., Evangelista, S., and Meli, A., The effect of urethane on histamine-induced contraction of guineapig tracheal smooth muscle. Experientia38 (1982) 1474–1476.

    Article  CAS  PubMed  Google Scholar 

  25. Mantelli, L., manzini, S., Mugelli, A., and Meli, A., The influence of some cardiodepressant drugs on the histamine induced restoration of contractility in potassium depolarized heart preparation. Archs int. Pharmacodyn. Ther.254 (1981) 99–108.

    CAS  Google Scholar 

  26. Manzini, S., Maggi, C. A., and Meli, A., A simple procedure for assessing norepinephrine induced cellular and extracellular Ca++ mobilization in rabbit ear artery. J. pharmac. Meth.8 (1982) 47–57.

    Article  CAS  Google Scholar 

  27. Manzini, S., Maggi, C. A., and Meli, A., Aminophylline-induced contraction of rabbit ear artery in high-K+ Ca++-free medium. J. Pharm. Pharmac.34 (1982) 195–196.

    Article  CAS  Google Scholar 

  28. Manzini, S., Maggi, C. A., and Meli, A., α-adrenoceptor subtypes and Ca++ mobilization in rabbit ear artery. J. Pharm. Pharmac.35 (1983) 584–589.

    Article  CAS  Google Scholar 

  29. Miller, F. N., and Wiegman, D. L., Anesthesia induced alteration of small vessels responses to norepinephrine. Eur. J. Pharmac.44 (1977) 331–337.

    Article  CAS  Google Scholar 

  30. Owen, D. A. A., Responses to pressor substances in conscious and anesthetized cats. Br. J. Pharmac.43 (1971) 668–670.

    Article  CAS  Google Scholar 

  31. Pappano, A. L., Calcium dependent action potential produced by catecholamines in guinea-pig atrial muscle depolarized by potassium. Circulation Res.27 (1970) 379–390.

    Article  CAS  PubMed  Google Scholar 

  32. Peng, T., Cooper, C. W., and Munson, P. L., The hypocalcemic effect of urethane in rats. J. Pharmac. exp. Ther.182 (1972) 522–527.

    CAS  Google Scholar 

  33. Pettinger, W. A., Tanaka, K., Keeton, K., Campbell, W. B., and Brooks, S. N., Renin release, an artifact of anesthesia and its implications in rats. Proc. Soc. exp. Biol. Med.148 (1975) 625–630.

    Article  CAS  PubMed  Google Scholar 

  34. Picotti, G. B., Carruba, M. O., Galya, M. D., Ravazzani, G., Bondiolotti, G. P., and Da Prada, M., Drug induced changes of plasma catecholamine concentrations, in: Radioimmunoassay of drug and hormones in cardiovascular medicine, pp. 133–148. Eds A. Albertini, M. Da Prada and B. A. Peskar. Elsevier North Holland Biomedical Press, Amsterdam 1979.

    Google Scholar 

  35. Severs, W. B., Keil, L. C., Klase, P. A., and Deen, K. C., Urethane anesthesia in rats: altered ability to regulate hydration. Pharmacology22 (1981) 209–226.

    Article  CAS  PubMed  Google Scholar 

  36. Spriggs, T. L. B., and Stockam, M. A., Urethane anesthesia and pituitary-adrenal function in the rat. J. Pharm. Pharmac.16 (1964) 603–610.

    Article  CAS  Google Scholar 

  37. Spriggs, T. L. B., The effects of anesthesia induced by urethane or phenobarbitone upon the distribution of peripheral catecholamines in the rats. Br. J. Pharmac. Chemother.24 (1965) 752–758.

    Article  CAS  Google Scholar 

  38. Strobel, G. E., and Wollman, H., Pharmacology of anesthetic agents. Fedn Proc.28 (1969) 1386–1403.

    CAS  Google Scholar 

  39. Thyrum, P. T., Inotropic stimuli and systolic transmembrane Ca++ flow in depolarized guinea-pig atria. J. Pharmac. exp. Ther.188 (1974) 166–179.

    CAS  Google Scholar 

  40. Volicer, L., and Loew, C. G., the effect of urethane anesthesia on the cardiovascular action of angiotensin II. Pharmacology6 (1971) 193–201.

    Article  CAS  PubMed  Google Scholar 

  41. Van Der Meer, C., Versluys-Broers, J. A. M., Tuynman, H. A. R. E., and Buur, V. A. J., The effect of ethylurethane on hematocrit, blood pressure and plasma-glucose. Archs int. Pharmacodyn.217 (1975) 257–275.

    Google Scholar 

  42. Watkins, R. W., and Davidson, I. W. F., Effects of competitive antagonists on phasic and tonic components of vascular smooth muscle contraction. Archs Int. Pharmacodyn.244 (1980) 200–210.

    CAS  Google Scholar 

  43. Wong, A. Y. K., A model of excitation contraction coupling of mammalian cardiac muscle. J. theor. Biol.90 (1981) 37–61.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmacology Department, Cardiovascular Section Research Laboratories, A. Menarini Pharmaceuticals, Via Sette Santi, I-50131, Florence, Italy

    C. A. Maggi, S. Manzini, M. Parlani & A. Meli

  2. C. R. F., Via Tito Speri, Pomezia, Rome, Italy

    C. A. Maggi, S. Manzini, M. Parlani & A. Meli

Authors
  1. C. A. Maggi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S. Manzini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. M. Parlani
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Meli
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Maggi, C.A., Manzini, S., Parlani, M. et al. An analysis of the effects of urethane on cardiovascular responsiveness to catecholamines in terms of its interference with Ca++ mobilization from both intra and extracellular pools. Experientia 40, 52–59 (1984). https://doi.org/10.1007/BF01959102

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01959102

Keywords

Search

Navigation