Abnormal platelet function and calcium handling in Dahl salt-hypertensive rats

Abstract

The effect of dietary salt on platelet function and Ca2+ homeostasis was studied in Dahl (DS) rats, a genetic model of salt-sensitive hypertension. DS rats were fed a high-salt (DSHS) or a low-salt diet (DSLS) for up to 4 weeks, and the effects of salt loading on systolic blood pressure, platelet P-selectin expression, and platelet Ca2+ homeostasis were measured. The high-salt diet increased blood pressure and markedly increased the amount of ionomycin (IM)-releasable Ca2+ in platelet intracellular stores (Ca2+/IM). The alteration in Ca2+ stores was not prevented when the hypertension was prevented by treatment with hydralazine and reserpine. The Ca2+ store filling during platelet exposure to 1 mmol/L Ca2+ for 5 minutes and the rate of sarcoplasmic/endoplasmic Ca2+ ATPase-dependent Ca45 uptake were higher in DSHS compared with that in DSLS. There was a decrease in thrombin-induced Ca2+ influx in platelets from DSHS; consistent with this, agonist-induced P-selectin expression was decreased. In DSLS, nitric oxide accelerated reloading of platelet Ca2+ stores after their emptying by thrombin but failed to do so in DSHS. These results indicate that in DS rats, a high-salt diet increases sarcoplasmic/endoplasmic Ca2+ ATPase activity and the Ca2+/IM but decreases the reuptake of Ca2+ caused by nitric oxide. Decreases in Ca2+ influx and platelet P-selectin expression might be explained by changes in intracellular Ca2+ stores in DSHS rats, which apparently is a heritable response to a high-salt diet.