1. Three patients with orthostatic hypotension due to peripheral autonomic neuropathy were studied. The diagnosis was based on severe hypotension during 60° head-up tilting and absence of the systolic pressure overshoot in phase IV of the Valsalva response. There was no clinical evidence for central nervous system involvement. Plasma noradrenaline levels were 50 and 90 pg/ml in two patients and below 25 pg/ml in one. Noradrenaline was unresponsive to head-up tilting. Heart rate did not change after atropine (2 mg intravenously) in two patients and it increased from 62 to 118 beats/min in the remaining patient after 1 mg. Thus the three patients had a peripheral sympathetic lesion which was accompanied with an efferent para-sympathetic lesion in two.
2. Infusion of isoprenaline in these patients showed supersensitivity for the chronotropic and vascular effects of this drug. Similar cardiac and vascular supersensitivity was observed for salbutamol. Cardiac chronotropic supersensitivity to prenalterol was less pronounced as compared with isoprenaline and salbutamol. The patients were treated with pindolol, 15 mg daily, divided in three doses. After 4 weeks' treatment pindolol was stopped and the infusions of isoprenaline and salbutamol were repeated 72 h after the last dose of pindolol (5 mg). The isoprenaline dose-heart rate response curve was shifted to the right by a factor of 10. The salbutamol dose-heart rate response curve was shifted by a factor of 45, whereas the prenalterol dose-heart rate response curve was shifted by a factor of only 3.
3. The observed chronotropic effects of salbutamol provide evidence for the existence of cardiac β2-adrenoceptors in man. Comparison of the cardiovascular responses after the non-selective β-adrenoceptor agonist isoprenaline, the β2-selective agonist salbutamol and the β1-selective agonist prenalterol suggests preferential β2-adrenoceptor sensitization in chronic autonomic failure, which can be reversed by treatment with the non-selective partial β-adrenoceptor agonist pindolol.