title: Ex vivo platelet studies following oral nisoldipine in normotensive insulin-dependent diabetics and non-diabetic controls.
abstract: The effect of 24 hours and 7 days treatment with nisoldipine (10 mg, twice daily) on platelet function was studied in 12 normotensive volunteers of whom six were insulin-dependent diabetics without clinical evidence of vascular complications. Platelet aggregation was assessed by platelet rich plasma (PRP) and whole blood (WB) techniques. In addition, the effect of nisoldipine on platelet hyperaggregability following exercise was assessed. After taking nisoldipine for 24 hours, in vitro platelet hypersensitivity to adenosine diphosphate was observed in PRP (p less than 0.01) and WB (p less than 0.01), to adrenaline in WB (p less than 0.03), and to collagen in PRP (p less than 0.02). After seven days treatment, platelet sensitivities to all agonists at rest in both PRP and WB showed no differences from pre-treatment values. Exercise-induced platelet hypersensitivity in WB to all three agonists was unchanged after nisoldipine treatment. Plasma noradrenaline and adrenaline concentrations increased after 24 hours treatment, although changes in agonist EC50s at 24 hours were not related to changes in plasma catecholamine levels. No effects of nisoldipine were observed on platelet thromboxane B2 release in PRP, or on plasma beta-thromboglobulin levels. No differences in the effects of nisoldipine were observed between diabetic and non-diabetic subjects. Nisoldipine treatment for seven days is not associated with altered platelet function, but platelet hypersensitivity is observed after treatment for 24 hours in both insulin-dependent diabetics and controls.
authors.affiliation: Academic Unit of Diabetes and Endocrinology, University College, Whittington Hospital, Highgate Hill, UK.
authors.forename: T J
authors.initials: TJ
authors.lastname: Hendra
authors.forename: J
authors.initials: J
authors.lastname: Oughton
authors.forename: J Y
authors.initials: JY
authors.lastname: Jeremy
authors.forename: C C
authors.initials: CC
authors.lastname: Smith
authors.forename: D J
authors.initials: DJ
authors.lastname: Betteridge
authors.forename: P
authors.initials: P
authors.lastname: Dandona
authors.forename: J S
authors.initials: JS
authors.lastname: Yudkin
mesh_terms: D000244:Adenosine Diphosphate / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000097:blood; D003094:Collagen / Q000494:pharmacology; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015737:Nisoldipine; D005082:Physical Exertion; D010974:Platelet Aggregation / Q000187:drug effects*; D010978:Platelet Factor 4 / Q000032:analysis; D012016:Reference Values; D013928:Thromboxane A2 / Q000097:blood; D001620:beta-Thromboglobulin / Q000032:analysis
chemical_list: D002395:Catecholamines; D001620:beta-Thromboglobulin; D010978:Platelet Factor 4; D015737:Nisoldipine; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen; D009543:Nifedipine; D004837:Epinephrine