Salt-induced plasma factor that inhibits platelet thromboxane A2 release and renal prostaglandin E2 production in rats.
This study examined the relationship between a plasma factor (or factors) that inhibits the release of thromboxane A2 from platelets and excessive salt intake in rats. The plasma factor, termed platelet inhibitory factor, was also characterized. The release of thromboxane A2 from thrombin-activated platelets was reduced in Wistar rats that were uninephrectomized and given 2% saline for a week, but not in rats with acute volume expansion. Platelet inhibitory factor was extracted from the plasma of these uninephrectomized and saline-loaded rats and partially purified using membrane sieves, reverse-phase high performance liquid chromatography (HPLC), modified straight-phase HPLC, and gel-permeation column chromatography. The molecular weight of the factor was about 4300 daltons by gel filtration method. The partially purified platelet inhibitory factor decreased the release not only of thromboxane A2, but also of prostaglandin E2 and prostaglandin D2 from thrombin-activated platelets. The factor inhibited the aggregation of human platelets induced by adenosine 5'-diphosphate (ADP), collagen, and thrombin, but not that by arachidonate. The platelet inhibitory factor reduced the activities of phospholipases A2 and C but did not affect the conversion of arachidonate to thromboxane A2. Furthermore, platelet inhibitory factor decreased prostaglandin E2 production in cultured renal cells, and platelet inhibitory factor-like activity was detected in kidney extract from the salt-loaded rats. These results suggest that platelet inhibitory factor is produced by chronic salt intake and involved in the functional alterations of the platelets and probably the kidneys, mainly through its inhibitory action on the liberation of arachidonate.
Uehara
Y
Y
Ishii
M
M
Ishimitsu
T
T
Sugimoto
T
T
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology; D001798:Blood Proteins / Q000494:pharmacology*; D055598:Chemical Phenomena; D002621:Chemistry; D002851:Chromatography, High Pressure Liquid; D015232:Dinoprostone; D007668:Kidney / Q000032:analysis / Q000378:metabolism*; D008297:Male; D011458:Prostaglandins E / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014020:Tissue Extracts / Q000494:pharmacology
D001798:Blood Proteins; D011458:Prostaglandins E; D014020:Tissue Extracts; C052788:platelet inhibitory factor; D012965:Sodium Chloride; D013928:Thromboxane A2; D015232:Dinoprostone