Decreased α₂-Adrenergic Receptors on Platelet Membranes from Diabetic Patients with Autonomic Neuropathy and Orthostatic Hypotension*

Abstract

Platelet adrenergic receptors were studied in normal subjects and diabetic patients with autonomic neuropathy to determine the relationship between adrenoreceptor status and orthostatic hypotension. The binding of [3H]clonidine and [3H]yohimbine to platelet membranes was measured in diabetic patients with autonomic neuropathy and orthostatic hypotension (n = 12) and without orthostatic hypotension (n = 11), diabetic patients without autonomic neuropathy (n = 12), and normal subjects (n = 9). Mean basal and standing plasma norepinephrine levels were not different in the four groups, and there was no relationship between orthostasis and norepinephrine responses. The diabetic patients with orthostatic hypotension had a significantly greater fall in mean blood pressure [31 +/- 2.8 (+/- SE) mm Hg] than any of the other three groups. Diabetic patients with diabetic autonomic neuropathy and orthostatic hypotension had a 30-40% decrease in number of platelet alpha 2-adrenergic receptors, as demonstrated by [3H]clonidine and [3H]yohimbine binding. The maximum number of binding sites for clonidine was 34 +/- 2.8 (+/- SE) fmol/mg protein in normal subjects, 27.4 +/- 3.4 in diabetic patients with neuropathy, 26 +/- 2.5 in diabetic patients with autonomic neuropathy without orthostatic hypotension, and 20.4 +/- 3.8 fmol/mg protein in diabetic patients with autonomic neuropathy with orthostatic hypotension (P less than 0.001). The maximum number of binding sites for yohimbine was 112 +/- 12.6 in normal subjects, 127 +/- 10 in diabetic patients without orthostatic hypotension, and 87 +/- 12.4 fmol/mg protein in patients with diabetic autonomic neuropathy with orthostatic hypotension (P less than 0.001). Reduced platelet alpha 2-receptors are associated with postural hypotension in diabetic autonomic neuropathy. If applicable to the postjunctional alpha 2-adrenergic receptor on sympathetic neurons, reduced vascular responses to changes in posture would be expected despite normal or enhanced norepinephrine secretion.

Decreased High Affinity State in Plateletα2-Adrenoceptors from Diabetic Patients with Orthostatic Hypotension

“…the lack of increase of plasma norepinephrine after 1-min standing) was observed in the group of diabetic patients without orthostatic hypotension. The present results agree with some data from Abrahm et al (14) who found that mean basal plasma norepinephrine levels were not different in the four groups studied (diabetic patients with autonomic neuropathy and orthostatic hypotension (group 1) or without orthostatic hypotension (group 2), diabetic patients without autonomic neuropathy (group 3) and normal subjects (group 4). Moreover, these authors, as did Pfeifer et al (13), indicated that there was no relationship between orthostasis and norepinephrine.…”

“…In diabetes mellitus, conflicting results were obtained since either no change (13) or a decrease (14) in total platelet « 2 -adrenoceptor number were reported.…”

Platelet activation in type 2 diabetes mellitus

“…Platelets have been shown to be targets of insulin action because they retain a functional insulin receptor capable of insulin binding and autophosphorylation [44]. Insulin is generally thought to reduce platelet responses to various agonists [45]. Decreased platelet insulin receptor number and affinity in subjects with T2DM have been reported [46], which suggested that reduced insulin sensitivity might account for platelet hyperactivity in T2DM, whereas other studies suggested the potential importance of insulin in maintaining normal platelet sensitivity to PGI 2 [26].…”

Action of Cleistanthins A and B on Alpha Adrenoceptors in Rats

“…Stimulation of alpha 2-adrenoceptors causes platelet aggregation and inhibition of insulin release. 8 Thus, our work was intended to explore the action of cleistanthins A and B on (a) alpha 2-adrenoceptors by studying their effect on platelet aggregation and insulin release, and (b) alpha 1-adrenoceptors using phenylephrine induced jejunal relaxation in adult male Wistar albino rats.…”