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Cell calcium handling and intracellular pH regulation in hereditary hypertriglyceridemic rats: reduced platelet
J Zicha1, J Kunes, M David-Dufilho
1Institute of Physiology, Academy of Science of the Czech Republic, Prague, Czech Republic.
Insights
Prague hereditary hypertriglyceridemic (HTG) rats, a model for hypertension and hyperlipidemia, exhibit reduced platelet responsiveness to thrombin stimulation. This indicates significant cell membrane alterations in these hypertensive rats.
Area of Science:
- Cardiovascular Research
- Membrane Physiology
- Hematology
Background:
- Genetic hypertension and dyslipidemia are linked to cell membrane alterations.
- Platelets and erythrocytes are crucial in cardiovascular health and disease.
- Understanding these alterations in animal models aids human disease research.
Purpose of the Study:
- To investigate cell membrane properties (calcium handling, pH regulation, thrombin response) in Prague hereditary hypertriglyceridemic (HTG) rats.
- To characterize platelets and erythrocytes in a novel genetic hypertension model with hyperlipidemia.
- To identify specific functional changes in HTG rat blood cells.
Main Methods:
- Comparative analysis of platelets and erythrocytes from HTG and control Wistar rats.
- Measurement of basal and stimulated cytosolic calcium (Ca2+) levels.
- Assessment of intracellular pH (pHi) regulation and buffering capacity.
- Evaluation of thrombin-induced responses, including Mn2+ influx via receptor-operated Ca2+ channels.
Main Results:
- No significant differences in basal cytosolic Ca2+ in platelets or erythrocytes between HTG and Wistar rats.
- Erythrocyte Ca2+ influx correlated positively with plasma triglycerides in both strains, with a less steep slope in HTG rats.
- HTG platelets showed diminished cytosolic Ca2+ response to thrombin and reduced thrombin-induced Mn2+ entry.
- Platelets from HTG rats exhibited a substantially reduced pHi response to thrombin stimulation.
Conclusions:
- Reduced responsiveness to thrombin stimulation is a key functional alteration in platelets of hypertensive hereditary hypertriglyceridemic rats.
- These findings highlight significant platelet dysfunction in this genetic model of hypertension and hyperlipidemia.
- Cell membrane changes in platelets may contribute to the pathophysiology of HTG rats.
Abstract:
Multiple cell membrane alterations have been described in humans and animals with various genetic forms of hypertension and/or dyslipidemia. The aim of our study was to characterize some properties of platelets and/or erythrocytes (cytosolic calcium handling, intracellular pH regulation and thrombin responsiveness) in a new model of genetic hypertension associated with hyperlipidemia-Prague hereditary hypertriglyceridemic (HTG) rats. There were no differences in basal cytosolic Ca2+ values in platelets or erythrocytes of HTG rats and control Wistar rats. Ca2+ influx into erythrocytes was also similar in HTG and control rats. In both strains Ca2+ influx correlated positively with plasma triglycerides. The slope of this relationship was less steep in HTG than in Wistar rats. Cytosolic Ca2+ response to thrombin stimulation was smaller in HTG platelets, which were also characterized by a major reduction of thrombin-induced Mn2+ entry through receptor-operated Ca2+ channels. Platelets of HTG rats had the same basal intracellular pHi values and similar buffering capacity as control rats but their pHi response to thrombin stimulation was substantially reduced. It can be concluded that reduced responsiveness to thrombin stimulation is a major alteration found in platelets of hypertensive hereditary hypertriglyceridemic rats.