Effects of beta-adrenoceptor blockade on heart rate and physiological tremor in diabetics with autonomic neuropathy. A comparative study of epanolol, atenolol and pindolol.

Eight diabetics with autonomic neuropathy were given single oral doses of epanolol (200 mg), atenolol (50 mg), pindolol (5 mg) and placebo in a double-blind randomised order at weekly intervals. Supine resting heart rate, physiological tremor and blood glucose were measured before, 2 and 4 h after dosing, and ambulatory heart rate monitored for 24 h. Supine resting heart rate was significantly lowered by atenolol both at 2 and 4 h, and increased on pindolol at 4 h. Heart rate was unaffected by epanolol compared with placebo. Heart rate during the 'waking' period (14.00-23.00 h) was lower than placebo after epanolol and atenolol but unaffected by pindolol. During the 'sleeping' period (23.00 h-08.00 h) heart rate was significantly increased by pindolol, lowered with atenolol and unaffected on epanolol. Pindolol significantly increased physiological tremor at 4 h. No differences were seen between epanolol, atenolol and placebo. Plasma glucose was significantly increased by pindolol 2 h after dosing. These results suggest that pindolol probably produces its partial agonist activity at both beta 1- and beta 2-adrenoceptors, while the partial agonist activity of epanolol is beta 1-selective. Despite abnormal cardiovascular reflex tests in these diabetics, the heart rate responses obtained in this study after beta-adrenoceptor blockade were surprisingly normal, and suggest that the concept of 'cardiac denervation' in diabetes requires modification.