1. Epstein SE, Robinson BF, Kahler RL, Braunwald E: Effects of beta adrenergic blockade on the cardiac response to maximal and submaximal exercise in man. J Clin Invest 44: 1745, 1965 2. Reybrouck T, Amery A, Billiet L: Hemodynamic response to graded exercise after chronic beta-adrenergic blockade. J Appl Physiol 42: 133, 1977 3. Franciosa JA, Johnson SM, Tobian LJ: Exercise performance in mildly hypertensive patients. Chest 78: 291, 1980 4. Bruce RA, Hossack KF, Kusumi F, Clarke LJ: Acute

more »

... ts of oral propranolol on hemodynamic responses to upright exercise. Am J Cardiol 44: 132, 1979 5. Pearson SB, Banks DC, Patrick JM: The effect of f-adrenoceptor blockade on factors affecting exercise tolerance in normal man. Br J Clin Pharmacol 8: 143, 1979 6. Hansson BG, Dymling JF, Hedeland H, Hulthin UL: Long term treatment of moderate hypertension with the beta,-receptor blocking agent metoprolol. Eur J Clin Pharmacol 11: 239, 1977 7. Leenen FMH, Coenen CHM, Zonderland M, Maas AHG: Effects of cardioselective and non-selective 3-blockade on dynamic exercise performance in mildly hypertensive men. Clin Pharmacol Ther 28: 12, 1980 8. Johnsson G: Influence of metoprolol and propranolol on hemodynamic effects induced by adrenaline and physical work. Acta Pharmacol Toxicol 36 (suppl V): 59, 1975 9. McSorley PD, Warren DS: Effects of propranolol and metoprolol on the peripheral circulation. Br Med J 3: 1598, 1978 10. Ablad B, Borg KO, Carlsson E, Ek L, Johnsson G, Malmfors T, Regardh CG: A survey of the pharmacological properties of metoprolol in animals and man. Acta Pharmacol Toxicol 36 (suppl V): 7, 1975 11. Johnsson G, Nykerg G, S81vell L: Influence of metoprolol and propranolol on hemodynamic effects induced by physical work and isoprenaline. Acta Pharmacol Toxicol 36 (suppl V): 69, 1975 12. Bruce RA: Exercise testing of patients with coronary heart disease. Principles and normal standards for evaluation. Ann Clin Res 3: 323, 1971 13. Aarons RD, Nies AS, Gal J, Hegstrand LR, Molinoff PB: Elevation of ,B-adrenergic receptor density in human lymphocytes following propranolol administration. J Clin Invest 65: 949, 1980 SUMMARY Diuretic-based antihypertensive drug therapy causes a disturbance in glucose tolerance and in serum lipid and lipoprotein concentrations. To determine the reversibility of the glucose intolerance and to identify mechanisms of the metabolic alterations, we examined a short glucose tolerance test and insulin, glycohemoglobin and lipid concentrations during the supervised withdrawal of long-term drug therapy in 35 patients with primary hypertension. An average of 7 weeks after stopping drugs, glucose tolerance and glycohemoglobin improved, total cholesterol decreased 18 mg/dl, triglyceride decreased 27 mg/dl, and the ratio of total to high-density lipoprotein cholesterol decreased (p < 0.01 for all variables vs treatment values). The changes in lipid concentrations from the treated to untreated state correlated with the changes in glycohemoglobin and indexes of glucose metabolism. The findings suggest that insulin resistance develops during drug therapy and disturbs both glucose and lipid metabolism. Attention to these alterations may provide directions for further control of atherosclerotic complications during the treatment of hypertension.