title: Calcium antagonist treatment, sympathetic activity and platelet function.
abstract: Calcium antagonists are a heterogeneous class of drugs, with different influences on neuro-hormonal activity and platelet function. Sympathetic nerves and platelets lack L-type calcium channels--calcium antagonist effects are thus related to indirect effects (cardiovascular and neurohormonal adaptation) and/or other actions on cellular mechanisms. Vascularly selective dihydropyridines usually elicit increases in heart rate, sympathetic counterregulation and renin release in the short term. In the long term, heart rate returns to basal levels, but sympathetic activity remains elevated in most studies. Heart-rate reducing calcium antagonists yield different results, with normal or reduced sympathetic activity on verapamil, and normal or elevated activity on diltiazem. Studies have mainly concerned venous plasma noradrenaline levels. There is therefore a need for more detailed studies to evaluate overall and regional sympathetic activity, and for heart rate variability studies. Antiplatelet effects of calcium antagonists are extensively documented in vitro, but such studies may reflect treatment effects poorly, and often involve high concentrations of the drugs. Clinical studies of platelet function also suggest antiplatelet effects, but the methods used have not always been optimal, and results have not been entirely consistent. More detailed and better controlled studies with in vivo-related techniques and fewer artefact influences from sampling, for example, are needed to fully evaluate calcium antagonists' effects on platelet function. Verapamil is most documented with regard to antiplatelet effects, but is also the calcium antagonist with the most varied possible mechanisms of action. Due to the heterogeneity of this class of drugs, documentation for one calcium antagonist cannot be generalized to also represent another with regard to neuro-hormonal or antiplatelet effects, especially when considering that these effects are not directly related to inhibition of Ca2+ influx via L-type calcium channels.
authors.affiliation: Department of Clinical Pharmacology, Karolinska Hospital, Stockholm, Sweden.
authors.forename: P
authors.initials: P
authors.lastname: Hjemdahl
authors.forename: N H
authors.initials: NH
authors.lastname: Wallén
mesh_terms: D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000503:physiopathology*; D006321:Heart / Q000187:drug effects / Q000294:innervation / Q000503:physiopathology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*
chemical_list: D002121:Calcium Channel Blockers