Decrease in beta-receptor density explaining the development of pindolol- and prenalterol-tolerance in orthostatic...

A 58-year-old woman with diabetic autonomic dysfunction was well treated for orthostatic hypotension with pindolol. After eight months however, symptoms recurred in spite of continued treatment with pindolol. Addition of prenalterol, a beta-blocking agent with very high intrinsic sympathomimetic activity, had a marked clinical effect on her orthostatic hypotension. Before treatment with prenalterol, stroke volume and left ventricular enddiastolic volume markedly decreased during tilt, as demonstrated by radionuclide angiography. After short-term prenalterol treatment, the orthostatic decreases of stroke volume and left ventricular end-diastolic volume were less pronounced. During continued prenalterol treatment, both symptoms and haemodynamic changes recurred in the erect position. Beta-receptor density in her lymphocytes decreased from elevated levels before prenalterol to subnormal levels, when the clinical effect had disappeared. The data suggest that the tolerance development to prenalterol may be explained by the decrease in beta-adrenergic receptor density.