A new method for studying platelets, based upon the low‐angle light scattering technique. 3. Aggregation hypersensitivity of platelets (ADP agonist) and search for corrective agents

Abstract

A new method for studying platelets based on low-angle light scattering has previously revealed that platelets taken from pregnant women with preeclampsia are hypersensitive to ADP, with aggregation developing at concentrations of 7–15 nmol l−1. The method has been applied to further studies in experimental toxicology and clinical pathology. Toxicological experiments with fluoroacetate (FA), an inhibitor of TCA cycle, showed that the platelet hypersensitivity could also be caused by energy depletion. In modeling experiments, the low-angle light scattering method was applied to assessment of potential corrective agents of the pathological states related to hypersensitivity of platelets. Sodium glutamate (SG) was shown to be a potent antiaggregantin vitro, and subsequentin vivostudies demonstrated that SG can apparently serve as anaplerotic agent and normalize the platelet status of rats intoxicated with FA. Donators of nitric oxide (NO), such as isosorbide-5′-dinitrate, can also normalizein vitrothe hypersensitive status of platelets taken from the patients with preeclampsia.

Polarographic and spectroscopic studies of the effects of fluoroacetate/fluorocitrate on cells and mitochondria

“…For example, when succinate or glutamate were used as respiratory substrates, FA did not affect mitochondrial functions in vitro. This is consistent with our recently reported data on sodium glutamate as anaplerotic agent, which was capable to recover blood platelet functions affected by FA in vitro and in vivo [6]. Earlier it was hypothesized that under action of FA exogenic glutamate could be utilized via glutamate dehydrogenase or transamination pathways [27,28].…”

“…The observed primary increase of cytosolic [Ca 2+ ] in cells exposed to FA is indicative of activation of calcium channels of plasma membrane; the process is not affected by FA and therefore does not require ATP, at least in glial cells [40]. Assuming this event to be common for various cells, it could explain hypersensitivity of platelets to ADP under exposure to FA [6]. Elevation of cytosolic [Ca 2+ ] level in cardiomyocytes can trigger an enhancement of the functional activity of cardiomyocytes: the resulting increase of Ca 2+ entry into endoplasmic reticulum could explain the data on enhanced amplitude and rate of Ca 2+ waves in cardiomyocytes.…”

“…Decrease in calcium level may be responsible for the hypocalcemic tetanus [4] that manifests itself in typical convulsions, blood clotting lesions and hypotension leading to vascular collapse and death [5]. Our recent experiments with FA in vitro and in vivo have shown that rat blood platelets become primarily hypersensitive to ADP with aggregation developing at very low ADP concentrations of 10-15 nM, followed by their transition to a refractory (insensitive) state [6].…”

Necrotic and apoptotic volume changes of red blood cells investigated by low‐angle light scattering technique

“…We have previously reported on a low-angle light scattering technique for investigating biological cells. The theoretical and experimental foundations of this methodology have been described, based mostly upon studies on blood platelets [14][15][16]. Ehrlich ascite tumor cells have also been the subject for investigation of intracellular signalling systems and ion channels using this technique [17].…”