Platelet thromboxane inhibition by plasma polypeptides in prehypertensive Dahl rats

Plasma from Dahl rats susceptible to salt-induced hypertension (Dahl S rats) contains inhibitory factors that reduce the release of thromboxane A2 from thrombin-activated platelets. Platelet-rich plasma from Dahl S rats on either low salt (0.11 or 0.3% NaCl) or high salt (4% NaCl) diets released about 50% less thromboxane A2 than comparable plasma from Dahl rats that are resistant to hypertension (Dahl R rats). This inhibitory activity was present even in the blood of 4-week-old completely normotensive Dahl S rats on a diet containing 0.11% low NaCl. The inhibitory activity could be transmitted to platelets of normal Sprague-Dawley rats by incubating these platelets in boiled and dialyzed plasma from Dahl S rats. Moreover, the inhibitory activity could be completely washed off the Dahl S platelets by incubation in Dahl R plasma. Thus, Dahl S plasma contains inhibitory factors that reduce platelet thromboxane A2 release. The factors are found in low concentrations even in Dahl R plasma; and in Dahl S or Dahl R plasma the factors are increased 25 to 32% by a 4% high NaCl diet. Digestion of Dahl S and Dahl R plasma with either trypsin or chymotrypsin destroyed the inhibitory factors, which have a molecular weight between 2,000 and 3,500. Twenty-four hours after bilateral nephrectomy, dialyzed plasma from both Dahl S and Dahl R rats was completely devoid of thromboxane A2 inhibitory activity. Thus, the factors appear to be heat-stable polypeptides either produced in the kidney or greatly influenced by the presence of renal tissue.(ABSTRACT TRUNCATED AT 250 WORDS)