Altered platelet alpha 2 adrenoreceptors in orthostatic hypotension.

Alpha 2 adrenergic agonists have been used to raise blood pressure in patients with idiopathic orthostatic hypotension (IOH). In an attempt to define the mechanism of action of these agents, radioligand binding of [3H]clonidine, an alpha 2 agonist, and of [3H]yohimbine, an alpha 2 antagonist, to human platelet membranes from a patient with IOH was performed to determine the maximum number (Bmax) and dissociation constant (KD) for this receptor. There was a marked decrease in receptor number in this patient when compared to normal subjects. In normal volunteers the specific binding of [3H]clonidine yielded a mean Bmax of 33 +/- 2 fmol/mg protein and a KD of 5.5 +/- 0.6 nM, while for the patient the Bmax was 20 fmol/mg protein and the KD was 7.4 nM. For [3H]yohimbine binding in normals, the Bmax was 165 +/- 12 fmol/mg protein and the KD was 4.0 +/- 0.5 nM, whereas for the patient the Bmax was 65 fmol/mg protein and the KD was 12.0 nM. Alpha 2 adrenergic agonists such as clonidine decrease blood pressure by stimulating central presynaptic alpha 2 sites, and thus inhibiting sympathetic activity. There are also alpha 2 adrenergic receptor sites postsynaptically on vascular smooth muscle. The presence of this receptor postsynaptically in a patient with a reduction of the presynaptic inhibitory sites could account for clonidine's pressor activity in patients with IOH. Further study of both alpha 2-adrenergic receptors in patients with IOH may be important in developing an understanding of central and peripheral mechanisms in the control of blood pressure.