| Autor: |
Pernollet MG; Pharmacologie, Université René Descartes, CNRS UMR 8604, Faculté de Médecine Necker, 156 rue de Vaugirard, 75015 Paris, France., Kunes J, Zicha J, Devynck MA |
| Jazyk: |
angličtina |
| Zdroj: |
Thrombosis research [Thromb Res] 2001 Oct 01; Vol. 104 (1), pp. 29-37. |
| DOI: |
10.1016/s0049-3848(01)00345-0 |
| Abstrakt: |
Prague hereditary hypertriglyceridemic (HTG) rats constitute a genetic model of hypertension associated with hyperlipidemia and insulin resistance. Various cell alterations, including changes in membrane dynamics, ion transport, and decreased platelet responses to thrombin have been observed in this strain. As hypertriglyceridemia appears to be associated with reduced endothelium-dependent vasodilation and platelet aggregation, we examined whether triglycerides could modulate cell responsiveness through changes in cyclic nucleotides in platelets of HTG rats. From the age of 6 weeks, these hypertensive animals were subjected for 10 weeks to interventions that modified circulating triglycerides levels (2.17+/-0.09 mmol/l), leading to their reduction (gemfibrozil treatment, 0.87+/-0.05 mmol/l) or elevation (high fructose intake, 3.23+/-0.07 mmol/l). Basal cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) contents were 15% and 48% lower in isolated platelets of HTG rats than in those of Lewis controls. cAMP level was further reduced in HTG rats subjected to high fructose intake. Irrespective of their plasma triglyceride levels, the thrombin-induced increase in platelet cGMP levels present in Lewis rats was absent in platelets of HTG rats. In contrast, no strain- or treatment-related differences were observed in the magnitude or kinetics of cGMP response to exogenous nitric oxide (NO). NO-induced cGMP and cAMP changes were associated in an opposite manner with trimethylamino-diphenylhexatriene (TMA-DPH) anisotropy, a biophysical parameter that reflects the microviscosity of the outer part of the cell membrane. Our results indicate that the attenuation of platelet responsiveness to thrombin in HTG rats represents a strain difference that cannot merely be due to a difference in plasma triglyceride levels. Platelet hyporesponsiveness to agonists such as thrombin in HTG rats cannot be explained by a change in levels of inhibitory cyclic nucleotides, since they were actually found to be low and not high. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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