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

Overview

Journal Experientia

Specialty Science

Date 1984 Jan 15

PMID 6692892

Citations 5

Authors

C A Maggi

S Manzini

M Parlani

A Meli

Affiliations

Soon will be listed here.

Abstract

Urethane (1 X 10(-2) - 1 X 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 beta-adrenoceptors at cardiac level.

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References

Mantelli L, Manzini S, Mugelli A, Ledda F . The influence of some cardiodepressant drugs on the histamine-induced restoration of contractility in potassium-depolarized heart preparations. Arch Int Pharmacodyn Ther. 1981; 254(1):99-108. View

van der Meer C, Tuynman H, Buur V . The effect of ethylurethane on hematocrit, blood pressure and plasma-glucose. Arch Int Pharmacodyn Ther. 1975; 217(2):257-75. View

Manzini S, Maggi C, Meli A . Aminophylline-induced contractions of rabbit ear artery in high-K+ Ca2+-free medium. J Pharm Pharmacol. 1982; 34(3):195-6. DOI: 10.1111/j.2042-7158.1982.tb04222.x. View

SPRIGGS T, Stockham M . URETHANE ANESTHESIA AND PITUITARY-ADRENAL FUNCTION IN THE RAT. J Pharm Pharmacol. 1964; 16:603-10. DOI: 10.1111/j.2042-7158.1964.tb07519.x. View

THYRUM P . Inotropic stimuli and systolic transmembrane calcium flow in depolarized guinea-pig atria. J Pharmacol Exp Ther. 1974; 188(1):166-79. View

Findell P, Larsen B, Benson B, Blask D . Mechanism of the effect of urethane on the secretion of prolactin in the male rat. Life Sci. 1981; 29(15):1515-22. DOI: 10.1016/0024-3205(81)90251-4. View

PETTINGER W, Tanaka K, Keeton K, Campbell W, Brooks S . Renin release, an artifact of anesthesia and its implications in rats. Proc Soc Exp Biol Med. 1975; 148(3):625-30. DOI: 10.3181/00379727-148-38597. View

de Jonge A, Santing P, Timmermans P, van Zwieten P . Functional role of cardiac presynaptic alpha 2-adrenoreceptors in the bradycardia of alpha-adrenoreceptor agonists in pentobarbitone-and urethane-anaesthetized normotensive rats. J Auton Pharmacol. 1982; 2(2):87-96. DOI: 10.1111/j.1474-8673.1982.tb00473.x. View

Watkins R, DAVIDSON I . Effects of competitive antagonists on phasic and tonic components of vascular smooth muscle contraction. Arch Int Pharmacodyn Ther. 1980; 244(2):200-10. View

10.

Kaufmann R, Bayer R, Furniss T, Krause H, 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 Mol Cell Cardiol. 1974; 6(6):543-59. DOI: 10.1016/0022-2828(74)90035-2. View

11.

Altura B, Altura B, Carella A, Turlapaty P, Weinberg J . Vascular smooth muscle and general anesthetics. Fed Proc. 1980; 39(5):1584-91. View

12.

Bailey H, Christian J . The distribution of N15 in rat tissues following the intraperitoneal administration of nitrogen-labeled urethan. J Am Pharm Assoc Am Pharm Assoc. 1952; 41(10):517-21. DOI: 10.1002/jps.3030411002. View

13.

Johansson B . Permeability characteristics of vascular smooth muscle cells as revealed by their osmotic responses to non-electrolytes. Acta Physiol Scand. 1969; 77(3):282-97. DOI: 10.1111/j.1748-1716.1969.tb04573.x. View

14.

Manzini S, Maggi C, Meli A . Alpha-adrenoceptor subtypes and Ca2+ mobilization in the rabbit ear artery. J Pharm Pharmacol. 1983; 35(9):584-9. DOI: 10.1111/j.2042-7158.1983.tb04338.x. View

15.

Altura B, Weinberg J . Urethane and contraction of vascular smooth muscle. Br J Pharmacol. 1979; 67(2):255-63. PMC: 2043884. DOI: 10.1111/j.1476-5381.1979.tb08674.x. View

16.

Maggi C, Meli A . Unsuitability of urethane anesthetized rats for testing potential beta-adrenoreceptor blockers. Experientia. 1982; 38(4):517-9. DOI: 10.1007/BF01952672. View

17.

Pappano A . Calcium-dependent action potentials produced by catecholamines in guinea pig atrial muscle fibers depolarized by potassium. Circ Res. 1970; 27(3):379-90. DOI: 10.1161/01.res.27.3.379. View

18.

SPRIGGS T . THE EFFECTS OF ANAESTHESIA INDUCED BY URETHANE OR PHENOBARBITONE UPON THE DISTRIBUTION OF PERIPHERAL CATECHOL AMINES IN THE RAT. Br J Pharmacol Chemother. 1965; 24:752-8. PMC: 1704032. DOI: 10.1111/j.1476-5381.1965.tb01631.x. View

19.

Wong A . A model of excitation-contraction coupling of mammalian cardiac muscle. J Theor Biol. 1981; 90(1):37-61. DOI: 10.1016/0022-5193(81)90121-1. View

20.

Hamon G, Worcel M . Mechanism of action of angiotensin II on excitation-contraction coupling in the rat portal vein. Br J Pharmacol. 1982; 75(3):425-32. PMC: 2071576. DOI: 10.1111/j.1476-5381.1982.tb09157.x. View