Effects of chronic treatment with adrenaline or propranolol on platelet function and c-AMP levels in the rat.
Most of our knowledge about the modulation of platelet function by catecholamines is based on observations of acute in vitro actions. Little is known about the effects of chronically elevated or reduced adrenergic stimulation of the platelets. We therefore treated rats for 8 weeks with either adrenaline or the beta-blocker propranolol. Adrenaline (0.5 mg.kg-1.d-1) continuously administered from subcutaneously implanted osmotic mini pumps caused an increase in the sensitivity of the platelets towards ADP as stimulating agent. In contrast, chronic application of propranolol (10 mg.kg-1.d-1) via the drinking water led to a reduction in platelet aggregability. For animals treated with adrenaline, in accordance with the results of the aggregation experiments, the levels of c-AMP found in platelet rich plasma were reduced, both basally (by 33%) and after stimulation of platelet adenylate cyclase with prostaglandin E1 (by 39%). For the propranolol treated animals, the basal c-AMP concentrations remained unchanged. The levels of c-AMP attained after stimulation with prostaglandin E1 were diminished to a similar extent as for the adrenaline treated animals (by 38%). Although the in vitro addition of adrenaline to platelet rich plasma causes a beta-adrenoceptor mediated inhibition of platelet aggregation in the rat, the simulation seen after chronic adrenaline exposure in vivo, which is associated with decreases in both basal and stimulated c-AMP levels, suggests a functional preponderance of alpha-adrenoceptors over beta-adrenoceptors on the rat platelets. Although intraplatelet metabolic changes (blockade of stimulated c-AMP formation) after chronic application of propranolol should have resulted in enhancement of platelet aggregability, an inhibition of aggregation was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
Terres
W
W
Department of Physiology, University of Munich, West Germany.
Becker
B F
BF
Schrödl
W
W
Gerlach
E
E
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000097:blood*; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004837:Epinephrine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D010975:Platelet Aggregation Inhibitors; D000244:Adenosine Diphosphate; D011433:Propranolol; D000242:Cyclic AMP; D004837:Epinephrine