title: Guanabenz, an antihypertensive centrally acting alpha2-agonist, suppresses morning elevations in aggregation of human platelets.
abstract: To determine whether the antihypertensive agent guanabenz affects the circadian rhythm in the hemorheologic properties of the platelet, we evaluated the aggregability of platelets collected from 11 healthy subjects in the morning and the evening after the oral administration of this agent, daily for 2 weeks. We analyzed platelet aggregation by the turbidimetric method. In an in vitro study, guanabenz, 10 nM-100 microM, did not affect platelet aggregation, whereas epinephrine induced platelet aggregation at an EC50 of 1.5 microM. The healthy volunteers demonstrated a diurnal variation in platelet aggregability that was high in the morning and low in the evening (66 +/- 10% and 56 +/- 11% respectively, of the percent platelet aggregation induced by epinephrine). The same variation was seen with the platelet aggregation induced by adenosine diphosphate (ADP) (62 +/- 8% [morning] vs. 51 +/- 7% [evening]). After the administration of guanabenz, platelet aggregability was significantly reduced in the morning compared with that before drug administration, when platelet aggregation was induced by epinephrine (49 +/- 9%, p < 0.05) or ADP (48 +/- 7%, p < 0.05), although the plasma levels of catecholamine were unchanged. A suppressive effect of guanabenz on platelet aggregability was observed in the evening, as the platelets were stimulated by epinephrine (38 +/- 9%, p < 0.05), but not by ADP (49 +/- 5%). Findings suggest that guanabenz mainly suppressed the morning enhancement in platelet aggregability, which contributes to the formation of intravascular thrombi. Thus, in addition to its antihypertensive actions, guanabenz may help to reduce the risk of vascular accidents, which frequently occur in the morning.
authors.affiliation: Department of Medicine and Gerontology, School of Medicine, Kyorin University, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Hayashi
authors.forename: H
authors.initials: H
authors.lastname: Sato
authors.forename: Y
authors.initials: Y
authors.lastname: Tanaka
authors.forename: J
authors.initials: J
authors.lastname: Tokuue
authors.forename: N
authors.initials: N
authors.lastname: Ishida
authors.forename: K
authors.initials: K
authors.lastname: Watanabe
authors.forename: K
authors.initials: K
authors.lastname: Kitamoto
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D000704:Analysis of Variance; D002940:Circadian Rhythm / Q000187:drug effects* / Q000502:physiology; D004837:Epinephrine / Q000494:pharmacology; D006143:Guanabenz / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects* / Q000502:physiology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects / Q000502:physiology
chemical_list: D000316:Adrenergic alpha-Agonists; D018341:Receptors, Adrenergic, alpha-2; D000244:Adenosine Diphosphate; D006143:Guanabenz; D004837:Epinephrine