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Decreased High Affinity State in Platelet ₂-Adrenoceptors from Diabetic Patients with Orthostatic Hypotension

Laboratoire de Pharmacologie Médicale et Clinique, INSERM U317, Centre Hospitalier Universitaire, Faculté de Médecine 37 allées J. Guesde, 31073 Toulouse Cedex, France
Service d'Endocrinologie et de Diabétologie (P.B., R.G., J.P.L.) Hôpital Purpan, 31059 Toulouse Cedex, France
Departamento de Farmacologia y Farmacotecnia (L.E.), Facultad de Medicina, Uniuersidad de Valencia Avd Blasco Ibanez 17, 46010 Valencia, Spain

Address correspondence and requests for reprints to: J. M. Senard, Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine, 37 allées J. Guesde, 31073 Toulouse Cedex, France.

Plasma catecholamine levels, total platelet ₂-adrenoceptor number and affinity state (using [³H]yohimbine binding) were investigated in insulin-dependent diabetic patients with (n = 12) or without (n = 10) orthostatic hypotension due to autonomic neuropathy as well as in normal control subjects (n = 6). Mean resting basal catecholamine values were similar in the three groups. One-minute standing elicited an increase in norepinephrine plasma level (but not in epinephrine plasma levels) in control group but not in diabetic patients (with or without orthostatic hypotension). The maximal number of platelet ₂-adrenoceptors (and K_D) calculated by [³H]yohimbine saturation experiments was similar in the three groups. The percentage of platelet ₂-adrenoceptors in high affinity state (inhibition experiments of [³H]yohimbine by UK14,3O4, a specific ₂-adrenergic full agonist) was significantly lower in diabetic patients with orthostatic hypotension (29.2 ± 5.3%) than in the other two groups. No significant difference was found between the control group (60.0 ± 2.0%) and diabetic patients without orthostatic hypotension (64.3 ± 3.1%). Since platelet ₂-adrenoceptors are thought to be a suitable index of vascular alpha-adrenoceptors, the decrease in platelet ₂-adrenoceptors in high affinity state could explain the occurrence of orthostatic hypotension in insulin-dependent diabetic patients. Multiple pathophysiological mechanisms underly orthostatic hypotension in insulin-dependent diabetic patients and include anomalies both in the sympathetic nervous system and in ₂-adrenoceptor coupling.

Received October 27, 1989.