CELL CALCIUM HANDLING AND INTRACELLULAR PH REGULATION IN HEREDITARY HYPERTRIGLYCERIDEMIC RATS - REDUCED PLATELET RESPONSE TO THROMBIN STIMULATION

Multiple cell membrane alterations have been described in humans and a nimals 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 reg ulation and thrombin responsiveness) in a new model of genetic hyperte nsion associated with hyperlipidemia - Prague hereditary hypertriglyce ridemic (HTG) rats. There were no differences in basal cytosolic Ca2values in platelets or erythrocytes of HTG rats and control Wistar rat s. Ca2+ influx into erythrocytes was also similar in HTG and control r ats. In both strains Ca2+ influx correlated positively with plasma tri glycerides. The slope of this relationship was less steep in HTG than in Wistar rats. Cytosolic Ca2+ response to thrombin stimulation was sm aller in HTG platelets, which were also characterized by a major reduc tion of thrombin-induced Mn2+ entry through receptor-operated Ca2+ cha nnels. Platelets of HTG rats had the same basal intracellular pH(i) va lues and similar buffering capacity as control rats but their pH(i) re sponse to thrombin stimulation was substantially reduced. It can be co ncluded that reduced responsiveness to thrombin stimulation is a major alteration found in platelets of hypertensive hereditary hypertriglyc eridemic rats.