SUMMARY Prostaglandin I, (PGI 2 , prostacyclin), a potent vasodilator synthesized by the blood vessels, has been postulated to play a role in hypertension. The purpose of our study was to test this hypothesis by monitoring the in vivo production of PGI 2 in Dahl salt-sensitive (S) and salt-resistant (R) rats under normal and high sodium intake. The 24-hour urinary excretion of two endogenous metabolites of PGI 2 , 2,3-dinor-6-oxo-PGF la , and 2,3-dinor-13,14-dihydro-6,15-dioxo-PGF la was measured by combined gas chromatography-mass spectrometry (GC-MS) and used as an index of the total production of PGI 2 by the animals. The pattern of urinary excretion of these two metabolites in the R and the S rats during the control period indicated that, under normal conditions, early in life the basal production of PGI 2 was the same in both groups of rats. Following the chronic administration of a high sodium diet (8.1 % sodium chloride, starting at 36 days of age), a significant and sustained increase in the urinary excretion of 2,3-dinor-6-oxo-PGF, a was documented in the R rats (from 37 ± 7 ng/24 hrs at age 35 days to 63 ± 7, 52 ± 4, and 56 ± 10 ng/24 hrs at 50,60, and 80 days, respectively), whereas the urinary levels of this metabolite decreased slightly in the S rats (from 41 ± 7 ng/24 hrs at age 35 days to 25 ± 5, 30 ± 6, and 28 ± 9 ng/24 hrs at 50, 60, and 80 days, respectively). During the same period, the R rats remained normotensive (103 ± 5 mm Hg, systolic pressure) while the arterial pressure of the S rats increased gradually (to 142 ± 8 and 180 ± 19 mm Hg at ages 60 and 80 days, respectively). After the age of 35 days, the urinary levels of 2,3-dinor-13,14-dihydro-6,15-dioxo-PGF la decreased sharply and independently of the diet in all groups, suggesting further transformation of this metabolite by co-oxidation, a well-known age-dependent phenomenon.Results of this study indicate that a high sodium intake is associated with a rise in the overall production of PGI 2 in the salt-resistant but not the salt-sensitive rats. This observation points to the existence of a defect in the production of PGI 2 in the salt-sensitive animals, a defect that is uncovered by high sodium intake and that may be causally related to the development of hypertension. (Hypertension 5: 701-705, 1983) KEY WORDS metabolite •• sodium chloride prostaglandin genetic hypertension • mass spectrometry P ROSTAGLANDIN I 2 , the major prostaglandin synthesized by the blood vessels and the renal cortex, has potent vasodilator and natriuretic properties, among others.1 -2 Evidence so far indicates that it is the most likely prostaglandin involved in the modulation of the vascular tone in vivo and, indirectly, the arterial pressure.3 ' 4 Consequently, it has been proposed that PGI 2 might play a role in hypertension, either as a cause or as an effect. One hypothesis is that From the
