Abnormal platelet function and calcium handling in Dahl salt-hypertensive rats.
The effect of dietary salt on platelet function and Ca(2+) 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 Ca(2+) homeostasis were measured. The high-salt diet increased blood pressure and markedly increased the amount of ionomycin (IM)-releasable Ca(2+) in platelet intracellular stores (Ca(2+)/IM). The alteration in Ca(2+) stores was not prevented when the hypertension was prevented by treatment with hydralazine and reserpine. The Ca(2+) store filling during platelet exposure to 1 mmol/L Ca(2+) for 5 minutes and the rate of sarcoplasmic/endoplasmic Ca(2+) ATPase-dependent Ca(45) uptake were higher in DSHS compared with that in DSLS. There was a decrease in thrombin-induced Ca(2+) influx in platelets from DSHS; consistent with this, agonist-induced P-selectin expression was decreased. In DSLS, nitric oxide accelerated reloading of platelet Ca(2+) 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 Ca(2+) ATPase activity and the Ca(2+)/IM but decreases the reuptake of Ca(2+) caused by nitric oxide. Decreases in Ca(2+) influx and platelet P-selectin expression might be explained by changes in intracellular Ca(2+) stores in DSHS rats, which apparently is a heritable response to a high-salt diet.
Li
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Vascular Biology Unit, Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, USA.
Adachi
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Bolotina
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Knowles
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Ault
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KA
Cohen
R A
RA
D000704:Analysis of Variance; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001792:Blood Platelets / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D006706:Homeostasis; D006830:Hydralazine / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D009569:Nitric Oxide / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D051381:Rats; D020303:Rats, Inbred Dahl; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000627:therapeutic use; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D012982:Sodium, Dietary / Q000008:administration & dosage / Q000009:adverse effects*; D014665:Vasodilator Agents / Q000627:therapeutic use
D000959:Antihypertensive Agents; D019007:P-Selectin; D012982:Sodium, Dietary; D014665:Vasodilator Agents; D006830:Hydralazine; D009569:Nitric Oxide; D012110:Reserpine; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D002118:Calcium