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 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.
Zicha
J
J
Institute of Physiology, Academy of Science of the Czech Republic, Prague, Czech Republic.
Kunes
J
J
David-Dufilho
M
M
Pernollet
M G
MG
Devynck
M A
MA
D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000235:genetics / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism; D017136:Ion Transport; D008345:Manganese / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D017208:Rats, Wistar; D017923:Sodium-Hydrogen Exchangers / Q000378:metabolism; D013917:Thrombin / Q000494:pharmacology*
D007473:Ion Channels; D017923:Sodium-Hydrogen Exchangers; D008345:Manganese; D013917:Thrombin; D002118:Calcium