Cell calcium handling and intracellular pH regulation in hereditary hypertriglyceridemic rats: Reduced platelet response to thrombin stimulation

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 Ca 2+ values in platelets or erythrocytes of HTG rats and control Wistar rats. Ca 2+ influx into erythrocytes was also similar in HTG and control rats. In both strains Ca 2+ influx correlated positively with plasma triglycerides. The slope of this relationship was less steep in HTG than in Wistar rats. Cytosolic Ca 2+ response to thrombin stimulation was smaller in HTG platelets, which were also characterized by a major reduction of thrombin-induced Mn 2+ entry through receptor-operated Ca 2+ channels. Platelets of HTG rats had the same basal intracellular pH i values and similar buffering capacity as control rats but their pH i 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.