Different effects of furosemide on alpha-adrenoceptors and on platelet aggregation in man.
The effect of a long-term administration of furosemide (2 x 30 mg/day for 3 weeks) on platelet alpha 2-adrenoceptor density and the fraction of high-affinity binding sites, as well as on platelet aggregation induced by adrenaline and ADP, was studied ex vivo in 8 normotensive volunteers. For comparison the in vitro effect of furosemide on platelet aggregation was also evaluated. Furosemide decreased alpha 2-adrenoceptor-density (P less than 0.01) and the fraction of high-affinity binding sites (P less than 0.05). Adrenaline-induced platelet aggregation was not altered ex vivo and in vitro. Furosemide inhibited ADP-induced platelet aggregation ex vivo (P less than 0.05) and in parallel in vitro (P less than 0.01) in a dose-dependent manner. The reduction of the density of alpha 2-adrenoceptors in the high affinity state may be of functional importance for the hemodynamic effects of furosemide. The inhibitory effect of furosemide on ADP-induced platelet aggregation ex vivo and in vitro, which is not related to the effects on adrenoceptors, seems to involve direct effects of furosemide on platelet function. It remains to be seen whether the latter effect is of clinical importance.
Kribben
A
A
Medizinische Klinik und Poliklinik, Freie Universität Berlin.
Fritschka
E
E
Sibold
M
M
Fassbender
M
M
Rothschild
M
M
Distler
A
A
Philipp
T
T
D000328:Adult; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*
D003692:Delayed-Action Preparations; D011942:Receptors, Adrenergic, alpha; D005665:Furosemide