Abstract
Treatment with β-blockers has been reported to be associated with the development of hypertriglyceridemia. The etiology, even the existence, of this phenomenon is controlverisal. The purpose of our study was to examine whether the nonselective β-blocker propranolol causes hypertriglyceridemia in the rat and whether its action is mediated by the modulation of lipoprotein lipase (LPL) messenger RNA (mRNA) accumulation or activity. LPL activity was assayed in fresh tissue by incubation with tritiated triglycerides. LPL mRNA was quantified in total RNA by slot-blot analysis using a mouse LPL complementary DNA probe. We have conducted three series of experiments in unanaesthetized rats in order to study the effects of different single doses of propranolol (1.5 to 6 mg i.p.) and different durations of treatment (15 min to 4 wk). We measured triglyceride and cholesterol levels in plasma as well as the LPL activity and mRNA levels in the heart and adipose tissue before and after propranolol administration. In these experiments we did not find any significant decrease in either the activity or the amount of mRNA of lipoprotein lipase nor was there any change in plasma lipids following treatment. Our results lead us to the conclusion that the nonselective β-blocker propranolol affects neither the activity nor, the mRNA level of LPL in the rat.
Similar content being viewed by others
Abbreviations
- cRNA:
-
complementary RNA
- LPL:
-
lipoprotein lipase
- mRNA:
-
messenger RNA
- TG:
-
triglycerides
References
Taskinen, M.-R. (1987) Lipoprotein Lipase in Hypertriglyceridemias, in Lipoprotein Lipase (Borensztajn, J., ed.) pp. 201–228, Evener Publishers, Chicago.
Lloyd-Mostyn, R.H., Lefevre, D., Lord, P.S., Doig, E., and Krikler, D.M. (1971) The Effect of Beta-Adrenergic Blocking Agents on Serum Lipids, Atherosclerosis 14, 283–287.
Bradford, M.M. (1976) A Rapid and Sensitive Method for the Quantitation of Microgram Quantities of Protein Utilizing the Principle of Protein-Dye Binding. Anal. Biochem. 72, 248–254.
Iverius, P.H., and östlund-Lindqvist, A.M. (1986) Preparation, Characterization, and Measurement of Lipoprotein Lipase, in Methods in Enzymology (Albers, J.J., and Segrest, J.P., eds.) Vol. 129, pp. 691–704, Academic Press, Orlando.
Chomczynski, P., and Sacchi, N. (1987) Single-Step Method of RNA Isolation by Acid Guanidium Thiocyanate-Phenol-Chloroform Extraction, Anal. Biochem. 162, 156–159.
Semenkovich, C.F., Chen, S.W., Wims, M., Luo, C.C., Li, W.H., and Chan, L. (1989) Lipoprotein Lipase and Hepatic Lipase mRNA Tissue Specific Expression, Developmental Regulation, and Evolution, J. Lipid Res. 30, 423–431.
Leren, P., Helgeland, A., Holme, I., Foss, P.O., Hjermann, I., and Lund-Larsen, P.G. (1980) Effect of Propranolol and Prazosin on Blood Lipids, The Lancet 2, 4–6.
Day, J.L., Metcalfe, J., and Simpson, C.N. (1982) Adrenergic Mechanisms in Control of Plasma Lipid Concentrations, Br. Med. J. 284, 1145–1148.
Goto, Y. (1984) Effects of Alpha-and Beta-Blocker Antihypertensive Therapy on Blood Lipids: A Multicenter Trial, Am. J. Med. 76, 72–78.
Ponti, G.B., Carnovali, M., Banderali, G., and Missaglia, A. (1983) Effects of Labetalol on the Lipid Metabolism in Hypertensive Patients, Curr. Ther. Res. 33, 466–471.
Tanaka, N., Sakaguchi, S., Oshige, K., Niimura, T., and Kanehisa, T. (1976) Effect of Chronic Administration of Propranolol on Lipoprotein Composition, Metabolism 25, 1071–1075.
Jansen, H., and Baggen, G.A. (1987) Effects of Doxazosin and Propranolol Administration on Lipoprotein Lipases in Cholesterol-Fed Rats, J. Cardiovasc. Pharmacol. 10 (Suppl. 9), S16-S20.
Dall'Aglio, E., Chang, H., and Reaven, G. (1984) Disparate Effects of Prazosin and Propranol on Lipid Metabolism in a Rat Model. Am. J. Med. 76, 85–88.
Krone, W., Müller-Wieland, D., and Greten, H. (1983) Regulation of Cholesterol Synthesis by Catecholamines in Human Mononuclear Leucocytes: Roles of Alpha-1, Alpha-2, Beta-1 and Beta-2 Adrenoreceptors, Arteriosclerosis 3, 492a.
Krone, W., Müller-Wieland, D., Nagele, H., Behnke, B., and Greten, H. (1987) Effects of Calcium Antagonists and Adrenergic Antihypertensive Drugs on Plasma Lipids and Cellular Cholesterol Metabolism, J. Cardiovasc. Pharmacol. 10, S199-S202.
Pinter, H.J., and Pattee, C.J. (1967) Effect of β-Adrenergic Blockade on Resting and Stimulated Fat Mobilization, J. Clin. Endocrinol. Metab. 27, 1441–1450.
Fager, G., Berglund, G., Bondjers, G., Elmfeldt, D., Lager, I., Olofsson, S.O., Smith, U., and Wiklund, O. (1985) Effects of Anti-Hypertensive Therapy on Serum Lipoproteins. Treatment with Metoprolol, Propranolol and Hydrochlorothiazide, Artery 11, 283–296.
Ferrara, L.A., Marotta, T., Rubba, P., De Simone, B., Soro, S., and Mancini, M. (1986) Effects of Alpha-Adrenergic and Beta-Adrenergic Receptor Blockade on Lipid Metabolism, Am. J. Med. 80, 104–108.
Waal-Manning, H.G. (1976) Metabolic Effects of β-Adrenoreceptor Blockers, Drugs 11, 121–126.
Barboriak, J.J., and Friedberg, H.D. (1973) Propranolol and Hypertriglyceridemia, Atherosclerosis 17, 31–35.
Hulsmänn, W.C., and Dubelaar, M.L. (1986) Lipoprotein Lipases and Stress Hormones: Studies with Glucocorticoids and Cholera Toxin. Biochim. Biophys. Acta. 875, 69–75.
Ball, K.L., Speake, B.K., and Robinson, D.S. (1986) Effects of Adrenaline on the Turnover of Lipoprotein Lipase in Rat Adipose Tissue. Biochim. Biophys. Acta 877, 399–405.
Ashby, P., Bennett, D.P., Spencer, I.M., and Robinson, D.S. (1978) Post-Translational Regulation of Lipoprotein Lipase Activity in Adipose Tissue, Biochem. J. 176, 865–872.
Palmer, W.K., and Kane, T.A. (1983) Hormone-Stimulated Lipolysis in Cardiac Myocytes, Biochem. J. 216, 241–243.
Friedman, G., Chajek-Shaul, T., Stein, O., Noe, L., Etienne, J., and Stein, Y. (1986) β-Adrenergic Stimulation Enhances Translocation, Processing and Synthesis of Lipoprotein Lipase in Rat Heart Cells, Biochim. Biophys. Acta 877, 112–120.
Robinson, D.S., Parkin, S.M., Speake, B.K., and Little, J.A. (1983) Hormonal Control of Rat Adipose Tissue Lipoprotein Lipase Activity, in The Adipocyte and Obesity: Cellular and Molecular Mechanisms (Angel, A., Hollenberg, C. H., and Roncari, D. A. K., eds.), pp. 127–136, Raven, New York.
Miller, W.C., Gorski, J., Oscai, L.B., and Palmer, W.K. (1989) Epinephrine Activation of Heparin-Nonreleasable Lipoprotein Lipase in Three Skeletal Muscle Fiber Types of the Rat, Biochem. Biophys. Res. Commun. 164, 615–619.
Carneheim, C., Nedergaard, J., and Cannon, B. (1984) β-Adrenergic Stimulation of Lipoprotein Lipase in Rat Brown Adipose Tissue During Acclimation to Cold, Am. J. Physiology 246, E327-E333.
Author information
Authors and Affiliations
Corresponding author
About this article
Cite this article
Gouni-Berthold, I., Oka, K., Berthold, H.K. et al. Failure of the nonselective β-blocker propranolol to affect lipoprotein lipase gene expression in the rat. Lipids 32, 943–947 (1997). https://doi.org/10.1007/s11745-997-0121-1
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11745-997-0121-1