[Is there any desensitization of presynaptic alpha 2-adrenergic receptors in hypertension? Experimental and clinical studies].
Several authors have discussed an alteration of adrenergic receptivity in arterial hypertension. De Champlain (Hypertension 1990; 8: S77-S85) suggested that postsynaptic alpha 1-adrenergic functions became dominant while beta-adrenergic functions are attenuated in arterial hypertension. However, the status of presynaptic alpha 2-adrenoceptors remains unknown. The present study investigates presynaptic alpha 2-adrenoceptors in hypertension through the measurement of plasma levels of noradrenaline after administration of yohimbine, an alpha 2-adrenoceptor antagonist, in essential hypertension. Yohimbine (0.2 mg/kg per os) induced a 73% increase of plasma levels of noradrenaline in hypertensive patients (n = 12) and a 178% one in normotensive subjects (n = 6, p < 0.05). A similar significant difference was found in experimental neurogenic hypertension observed in awake dogs 3 weeks after sinoaortic denervation: the increase in plasma concentrations of noradrenaline after yohimbine (0.5 mg/kg i.v.) was +279% in hypertensive versus +642% in normotensive dogs (p < 0.05). The results show that the magnitude of the yohimbine-induced sympathetic activation is lower in hypertensives than in normotensives. They suggest the existence of a presynaptic alpha 2-adrenoceptor desensitization in arterial hypertension. The abnormality of this presynaptic inhibitory mechanism can increase the sympathetic tone and help to develop and maintain arterial hypertension.
Laboratoire de pharmacologie médicale et clinique, INSERM U 317, Centre hospitalier universitaire Purpan, faculté de médecine, Toulouse.
C
C
Damase-Michel
G
G
Tavernier
M E
ME
Llau
F
F
Chollet
J M
JM
Sénard
H
H
Bagheri
M A
MA
Tran
G
G
Houin
B
B
Guiraud-Chaumeil
J L
JL
Montastruc
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D003714:Denervation; D004195:Disease Models, Animal; D004285:Dogs; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D008875:Middle Aged; D015016:Yohimbine
D000317:Adrenergic alpha-Antagonists; D015016:Yohimbine
Existe-t-il une désensibilisation des récepteurs alpha 2-adrénergiques présynaptiques dans l'hypertension artérielle? Etudes expérimentales et cliniques.