Effect of beta-blocking drugs on red cell adhesive and rheological properties.
Abnormal cell-cell interactions at the vessel wall play an important role in the development of microvascular occlusions. Since beta-blocking drugs have been implicated in the long-term and short-term prevention of myocardial infarction, we investigated the possibility that these drugs might exert their action by interfering with red cell-endothelial interactions. 51Cr-labeled, washed erthrocytes were added to confluent monolayers of cultured human vascular endothelial cells. After incubation at 37 degrees C, the nonadherent red cells were removed by sequential washing. When red cells were pretreated by cardioselective or noncardioselective beta-blocking drugs (e.g., metoprolol and propranolol), significantly fewer erythrocytes remained adherent to the endothelial monolayers after repeated washing. Pretreatment of the endothelium did not result in decreased adherence, indicating that the inhibitory action of beta-blockers is exerted on the red cell itself. The specificity of red cell-endothelial interactions is illustrated by the finding that erythrocytes adhere significantly less to plastic surfaces. In parallel studies, we have shown that beta-blockers significantly both diminish erythrocyte viscosity and increase erythrocyte deformability. The precise mechanisms of cellular action by which beta-blockers exert these actions remain unknown. Differences in beta-receptor subtypes do not seem to be involved, but complex metabolic changes leading to alterations in physiological properties of the red cell membrane cannot be excluded. Finally, our results suggest that the presumed beneficial effects of beta-blockade in various prethrombotic conditions (e.g., hypertension, angina pectoris, reinfarction) may be partly due to the interference of these drugs with the normal and abnormal adhesive and rheological properties of human erythrocytes.
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D001809:Blood Viscosity / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D004727:Endothelium / Q000166:cytology; D004837:Epinephrine / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D008790:Metoprolol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D014462:Ultrafiltration
D000319:Adrenergic beta-Antagonists; D011433:Propranolol; D008790:Metoprolol; D004837:Epinephrine