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.