vivo production of prostaglandin I2 in Dahl salt-sensitive and salt-resistant rats. Hypertension

SUMMARY Prostaglandin I, (PGI2, 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 PGI2 in Dahl salt-sensitive (S) and salt-resistant (R) rats under normal and high sodium intake. The 24-hour urinary excretion of two endogenous metabo-lites of PGI2, 2,3-dinor-6-oxo-PGFla, and 2,3-dinor-13,14-dihydro-6,15-dioxo-PGFla was measured by combined gas chromatography-mass spectrometry (GC-MS) and used as an index of the total production of PGI2 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 PGI2 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-PGFla decreased sharply and independently of the diet in all groups, suggesting further transforma-tion 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 PGI2 in the salt-resistant but not the salt-sensitive rats. This observation points to the existence of a defect in the production of PGI2 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