SUMMARY A polypeptide fraction isolated from the urine of nonnotenslve subjects lowers the blood pressure (BP) in a rabbit bioassay (mean BP decrease 33.8% ± 0.6%, SEM). Patients with primary hypertension exhibit reduced or no activity (mean BP decrease 8.8% ± 1.2%). In contrast, patients with secondary forms of hypertension show activity like nonnotensives (mean BP decrease 33.4% ± 1.0%). Tbe results of the bioassay in tbe two patient groups correlate well with the family inddence of hypertension (68% and 37% for primary and secondary hypertension respectively). Cases with borderline hypertension fall into two groups; a larger one with vasoactivity in the bioassay and lower family inddence of hypertension; and a smaller group reacting like patients with primary hypertension. Only the latter group may represent an initial stage of primary hypertension. In nonnotenslve children and young men, an inactive fraction was found in 31% and 28% respectively. These inactive groups had twice the family inddence of hypertension compared to the groups with vasoactivity. These results suggest the existence of a possible genetic marker of primary hypertension and may offer the possibility to detect the disease before its manifestation. ical markers of the postulated genetic abnormality have been established. The urine of normotensive subjects contains significant amounts of low molecular weight kinins and kallikrein.8 In addition, we have previously reported the existence of a vasoactive polypeptide fraction in the urine of normotensive human beings irrespective of age and sex. 4 "* This fraction was shown to dilate the vessels of the general circulation and to retain activity in an isolated vessel preparation, while it was inactive in the pulmonary circulation, the isolated heart, or intestinal preparation.' 1 T As reported earlier, a similar, crude polypeptide fraction isolated from the urine of patients with primary hypertension did not lower the blood pressure (BP) in the bioassay. 4 ' B In view of these findings, we attempted to isolate and characterize the polypeptide fraction in a greater number of patients with different types of hypertension. In addition, we carried out studies on samples of the normal population. Since altered kallikrein excretion has been reported in patients with hypertension,"' * we also measured the kallikrein content in the urinary polypeptide fraction under study.

We have purrfied vasoactrve polypetrdes from the urme of normotensrve humans by gel filtratron on Sephadex G150 superfine romc exchange chromatography on DEAE-cellulose and rsoelectnc focusing m polyacrylamrde gels usmg a pharmalyte pH range of 2.5-5.0 The purified polypetrde fraction yrelded four bands by rsoelectrrc focusing with rsoelectrrc pomts at pH 4 15, 4 05, 3 9 and 3 8 On dodecyl sulphate/polyacrylamide gel electrophoresrs (page) two bands appeared, one small band wrth a M, of 29 000 and one broad band rangmg from M,49 000 to M,42 500 The polypetrdes lower the blood pressure of rabbits m a bioassay and cleave D-valyl-L-leucyl-L-argmme-4-mtroanihde with a specrfic actrvrty comparable to that of kalhkrem