Decreased high affinity state in platelet alpha 2-adrenoceptors from diabetic patients with orthostatic hypotension.
Plasma catecholamine levels, total platelet alpha 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 alpha 2-adrenoceptors (and KD) calculated by [3H]yohimbine saturation experiments was similar in the three groups. The percentage of platelet alpha 2-adrenoceptors in high affinity state (inhibition experiments of [3H]yohimbine by UK14,304, a specific alpha 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 alpha 2-adrenoceptors are thought to be a suitable index of vascular alpha-adrenoceptors, the decrease in platelet alpha 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 alpha 2-adrenoceptor coupling.
Senard
J M
JM
Laboratoire de Pharmacologie Médicale et Clinique, INSERM U317, Centre Hospitalier Universitaire, Faculté de Médecine, Toulouse, France.
Barbe
P
P
Estan
L
L
Guimbaud
R
R
Louvet
J P
JP
Berlan
M
M
Tran
M A
MA
Montastruc
J L
JL
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism*; D000068438:Brimonidine Tartrate; D002462:Cell Membrane / Q000378:metabolism; D003920:Diabetes Mellitus / Q000097:blood / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000097:blood / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007024:Hypotension, Orthostatic / Q000097:blood*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011311:Pressoreceptors / Q000503:physiopathology; D011810:Quinoxalines / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D015016:Yohimbine / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D000068438:Brimonidine Tartrate; D006442:Glycated Hemoglobin; D011810:Quinoxalines; D011942:Receptors, Adrenergic, alpha; D015016:Yohimbine