This research proposal has two main objectives: 1) To devise a means for determining in childhood which persons are destined to become adult hypertensives and which are not, and 2) To gain further information about the chemical identity and physiological role of a newly found large plasma polypeptide which is present in high concentration in very young Dahl S rats on a very low NaCl diet long before they become hypertensive and is found on very much lower concentration in very young Dahl R rats that will never become hypertensive. When the """"""""factor"""""""" in Dahl S plasma is concentrated 6-fold, it will act on thrombin-activated platelets to reduce their release of thromboxane A2(TXA2) to 1/10 that which is found when platelets are incubated in concentrated Dahl R plasma. If this were the situation in hunans, finding the concentration of the """"""""factor"""""""" in a child's plasma would give a strong indication whether or not he or she is destined to become hypertensive. It is proposed to search for the chemical identity of this plasma factor using Sephadex columns, HPLC, and two-dimensional polyacrylamide gels, amino acid analysis and amino acid sequencing. The plasma concentration of the """"""""factor"""""""" will be studied in DOC hypertension and in 1 kidney, 1 clip and 2 kidney, 1 clip Goldblatt hypertensions. The kidneys will be removed and in other studies the adrenals will be removed to determine the effect of these factors on the level of the """"""""factor"""""""" in Dahl S rats. 4 separate brain lesions will be made in 4 separate studies to determine if this will affect the concentration of the """"""""factor"""""""" in Dahl S rats. An F2 generation of Dahl S and R rats will be bred to correlate the level of the BP with the level of the factor. Finally, children of hypertensive parents vs children of normotensives will be studied for the plasma level of the """"""""factor"""""""". Other markers of the pre-hypertensive state will be sought in both children and in Dahl S and R rats. 1) Are the urinary prostaglandins, thromboxane B2 elevated and the urinary 6-Keto-PGF1Alpha (from prostacyclin) depressed in pre-hypertensive children and rats? 2) Will small levels of excess albuminuria in children signal future hypertension? 3) Do borderline hypertensive children or rats have a limited rise of GFR after a big protein meal? 4) Does the K efflux from lymphocytes incubated at 4 degrees C indicate future hypertension? Several early factors may predict adult hypertension.
