Abnormalities of platelet function in hypertension and diabetes.

Abstract

SUMMARY The increased frequency of hypertension in diabetes and of abnormalities of carbohydrate metabolism in hypertension are now well established. It is conceivable that the high coincidence of the two diseases is based on a common metabolic defect. Studies of platelets permit the evaluation of the stimulatory, phospholnositol-linked and the inhibitory, cyclic adenosine 3',5'-monophosphatedependent pathways of cell activation. Furthermore, platelets may be relevant for the development of angiopathy through their contents of growth factors. Abnormalities of platelet aggregation have been demonstrated in hypertension and diabetes. They are accompanied by exaggerated stimulation of adenylate cyclase in hypertension and abnormal activity of cyclic guanosine 3',5'-monophosphate phosphodiesterase in diabetes. Defective function of platelets is also observed in patients and animals when the two diseases are present at the same time. Both increased and decreased aggregation have been described in these two diseases in the literature. The apparent discrepancies may be due to different types of platelet preparation, evaluation of aggregation, evolution of defect with age, and form of the disease. Integrated studies of biochemical mechanisms responsible for cell activation are needed to characterize the exact defect present in diabetes and hypertension in platelets. As in other countries, hypertension in Canada is present in about 50% of diabetics and the rate of occurrence of diabetes is high among hypertensives (Table 1). In our own clinics at the Clinical Research Institute of Montreal and Hotel-Dieu Hospital, we have noted that 43% of diabetics have increased blood pressure and 31% of hypertensives have abnormal blood glucose levels.

Defective protein phosphorylation associated with hypofunctions in stroke-prone spontaneously hypertensive rat platelets.

“…23 In addition, these hypofunctions were demonstrated with any of the platelet preparations 28 (whole blood, platelet rich plasma, gel-filtered, and washed) and also with various aggregating agents. 1 The results obtained by Hamet et al 33 coincides well with ours. In contrast, Koutouzov et al 34 and Huzoor-Akbar and Anwer 35 have reported increased aggregation in platelets of SHR.…”

“…In this paper the mechanism of the defective protein phosphorylation related to hypoaggregability was investigated. In 1988, HuzoorAkbar and Anwer 33 reported an increase in thrombininduced protein phosphorylation, and Koutouzov et al 34 observed an increase in phospholipase C activity in thrombin-stimulated platelets of SHR. These results contradict ours that were obtained in platelets of SHRSP.…”

Transport of Cyclic Nucleotides and Estradiol 17-β-d-Glucuronide by Multidrug Resistance Protein 4

“…One proposed function is that it contributes to the modulation of cyclic nucleotide signaling by reducing intracellular levels of these second messengers. In support of this notion is the consistent observation that triggered elevations in intracellular cyclic nucleotide levels are associated with enhanced cellular efflux (52)(53)(54)(55)57). A second proposed function for efflux is in provision of extracellular cAMP involved in intercellular signaling.…”

Preoperative triglycerides predict post-coronary artery bypass graft survival in diabetic patients: a sex analysis.

“…Triglyceride-rich lipoproteins in the vessel wall and associated cells (23) lead to fatty streaks, which are noted in saphenous vein grafts within 18 months post-CABG (24). An enhanced blood coagulation-fibrinolytic system may be associated with both serum triglyceride concentrations (25) and the presence of diabetes (5,26). In the postmenopausal period (the typical life-cycle phase for women in this study), hepatic lipase activity rises because of an absence of estrogen, leading to an increase in small dense LDLs (27), particularly observed in the presence of a high concentration of triglyceride particles (28).…”