The effect of streptozocin-induced diabetes on platelet aggregation as determined by impedance aggregometry and platelet secretion: a possible role for nitric oxide.
Previous studies from our laboratory showed that diabetes increases platelet aggregation in rats, but only in washed platelets. In the present study, we evaluated platelet aggregation coupled with adenosine triphosphate (ATP) release in normal and diabetic rats using a whole blood electrical aggregometer. Additionally, we investigated the role of endothelium-derived relaxing factor, or nitric oxide, in the platelet reactivity in diabetic rats. Rats were made diabetic using streptozocin, 55 mg/kg. After 1 month the rats were anesthetized, and arterial blood samples were collected directly into sodium citrate solution 3.8%. Platelet counts and mean platelet volumes were determined. Platelet aggregation, disaggregation, and ATP release in response to adenosine diphosphate (ADP), collagen, and arachidonic acid were measured. Platelet aggregation in response to ADP, collagen, and arachidonic acid was not different in diabetic rats when compared with that in controls. However, ATP release in response to ADP was significantly increased in diabetic rats. Platelets from diabetic animals were significantly larger than those of controls. Nitro-L-arginine methyl ester, a nitric oxide synthase inhibitor, decreased platelet aggregation in response to ADP in the normal animals, but not in the diabetic animals. However, arginine-induced nitric oxide production decreased platelet aggregation and enhanced the occurrence of disaggregation in platelets from both normal and diabetic rats. From these studies, we conclude that platelet aggregation in diabetic rats is not different using whole blood electrical aggregation, but platelet ATP secretion is significantly enhanced. Additionally, nitric oxide may modulate the platelet aggregation, disaggregation, and ATP secretory response. However, it does not appear to be a major factor in the altered aggregation responses in diabetic rats.
Judge
S
S
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.
Mammen
E
E
Dunbar
J C
JC
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood* / Q000139:chemically induced; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D016718:Arachidonic Acid; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D003094:Collagen