Adrenal Steroidogenesis in Rats Bred for Susceptibility and Resistance to the Hypertensive Effect of Salt

Adrenal steroidogenesis was studied in rats specifically bred for resistance (R) or susceptibility (S), respectively, to the hypertensive effects of salt. S compared to R rats showed higher 18-hydroxydeoxycorticosterone (180HDOC) levels in adrenal venous blood and peripheral plasma. S rat adrenals in vitro produced twice as much 180H-D0C as R rats. The higher 18-hydroxylase activity in S rats was exactly offset by lower llβ-hydroxylation in S rats. This gave rise to characteristic ratios of 18OH-DOC/corticosterone (B) formed in vitro by S and R rat adrenals. Salt feeding did not alter these results. in vitro data from individual rats of several strains suggest that rats fall into 2 phenotypes: those with a high 180H-D0C/B ratio of .65–.80 (S-type) and those with a low ratio of .2–.45 (R-type). Both phenotypes were seen in Sprague-Dawley rats, the strain from which S and R rats were developed. It was concluded that the clear separation of these 2 phenotypes by the selective breeding program which produced the S and R strains was evidence for an effect of 180H-D0C (or the 180H-D0C/B ratio) on blood pressure. Both the spontaneously hypertensive rats of Okamoto and Aoki, and unselected, normotensive Wistar rats had high 180H-D0C/B ratios (S-type). From this fact and other previously published work, it was emphasized in the Discussion that the high 180H-D0C/B ratio of S rats does not in itself explain the total susceptibility of rats to hypertension. In terms of the 180H-D0C/B ratio, it was the low ratio of the resistant rats that appeared to be unique. It was concluded that genetic control of the 180H-D0C/B ratio is probably one of the several genes involved in blood pressure regulation in the rat. (Endocrinology88: 52, 1971)