Inhibitory effects of cardiotonic pills on platelet function in dogs fed a high-fat diet.
Insulin resistance and the consequent metabolic disorders are associated with a state of platelet hyperactivity. Oxidative stress is responsible for the persistent platelet activation. We sought to study the inhibitory effect of cardiotonic pills, an oral herbal component, on platelet function in a dog model with insulin resistance induced by high-fat feeding. We fed 18 dogs with a high-fat diet and six dogs with normal chow as control for 6 months. Then, six dogs were fed with a high-fat diet and received additional aspirin (250 mg/day), and another six dogs received additional cardiotonic pills (1,000 mg/day) for 4 months. Time-course changes in metabolic parameters and platelet function were detected. After high-fat feeding for 6 months, 18 dogs developed a series of metabolic disorders including obesity, dyslipidemia, oxidative stress and insulin resistance. In addition, a platelet hyperactivity state, characterized by increased agonist (arachidonic acid, ADP and collagen) induced platelet aggregation, platelet expression of adhesion molecules (P-selectin and GP IIb/IIIa), and platelet intracellular calcium concentration, was indicated. Cardiotonic pills showed a significant antioxidative activity by presenting an increase in plasma superoxide dismutase and decrease in erythrocyte glutathione, as well as a lipid-lowering effect (decrease in both plasma cholesterol and triglyceride). Either aspirin or cardiotonic pills could significantly reverse the platelet hypersensitivity and hyperfunction. Compared with aspirin, cardiotonic pills showed a more exaggerated inhibitory effect on platelet function (a significantly decreased collagen-stimulated platelet aggregation, and expression of adhesion molecules). In conclusion, cardiotonic pills inhibited platelet hyperfunction in dogs with insulin resistance. This inhibitory effect may mainly be explained by antioxidative activity and metabolic control.
Zhang
Lei
L
Department of Cardiology, Tianjin 254th Hospital, Affiliated Hospital of the Medical College of Nankai University, China. zhanglei254@hotmail.com
Zheng
Jun
J
Li
Hui-Min
HM
Meng
Yong-Xia
YX
D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004041:Dietary Fats / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004285:Dogs; D004304:Dosage Forms; D007333:Insulin Resistance; D009765:Obesity / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D019007:P-Selectin / Q000096:biosynthesis / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000096:biosynthesis / Q000187:drug effects
D002316:Cardiotonic Agents; D004041:Dietary Fats; D004304:Dosage Forms; D019007:P-Selectin; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D001241:Aspirin; D002118:Calcium