Increased vascular beta2-adrenoceptor responsiveness in autonomic dysfunction.

Responsiveness to the vasopressor, vasodepressor and chronotropic effects of several sympathomimetic amines was assessed in 12 patients with severe autonomic dysfunction and in 8 age-matched control subjects. The patients with autonomic dysfunction showed a profound increase in responsiveness to both isoproterenol and phenylephrine as compared with control subjects. The mean bolus dose of isoproterenol required to increase heart rate by 25 beats/min was 0.9 + 0.2 microgram in the patients and 5.4 + 2.1 micrograms in the control subjects. The dose of isoproterenol required to reduce mean blood pressure by 25 mm Hg was 0.3 + 0.2 and 5.2 + 1.8 micrograms, respectively. Thus, although there is a 6-fold increase in responsiveness to the chronotropic effect of isoproterenol in autonomic dysfunction, the responsiveness to the drug's depressor effect is increased 17-fold. This enhanced depressor sensitivity is quite marked, even with oral beta-adrenoceptor agonists. Beta-adrenoceptor agonists must be used with caution in conditions associated with autonomic dysfunction if dangerous hypotension is to be avoided.