18-Hydroxy-Deoxycorticosterone Secretion in Experimental Hypertension in Rats
Adrenal steroidogenesis was studied in vitro and in vivo in rats which have been specifically bred for susceptibility (S strain) or resistance (R strain) to the hypertensive effects of salt. A marked quantitative difference was found between S and R rats in the adrenal biosynthetic pathways which are subsequent to deoxycorticosterone (DOC). There was a twofold difference in the ability to 18-hydroxylate DOC to form 18-hydroxy-deoxycorticosterone (18OH-DOC) with the greater activity in the S rats. This increment in 18-hydroxylation of DOC in S over R rats was offset by an equal decrement in 11β-hydroxylation of DOC to form corticosterone (B) in S compared with R rats. These alterations in metabolic pathways gave rise to characteristic 18OH-DOC/B ratios for S and R animals that were obvious both in vitro and in vivo.
The data suggest, therefore, that in selectively breeding rats on the basis of blood pressure response to salt, a gene (or genes) which affects the 18OH-DOC/B ratio has been segregated in the S and R strains. Although this segregation is in itself good evidence for an effect of 18OH-DOC (or 18OH-DOC/B ratio) on blood pressure in rats, it was also emphasized that there is evidence for more than one gene affecting blood pressure in rats. Thus, the steroid difference described is likely to be controlled by only one of several genes affecting the quantitative character of blood pressure. Comparison of 18OH-DOC/B ratios in S and R strains with other strains of rats showed that the high ratio in S rats was quite common, but that the low ratio in R rats was rather unique. Thus, it seems that the low 18OH-DOC/B ratio of R animals connotes resistance to salt, while the higher ratio in S and unselected strains probably only connotes normal susceptibility to salt. The extreme sensitivity of S rats to salt must therefore be accounted for by other genes.
- salt susceptibility
- salt resistance
- adrenal steroidogenesis
- adrenal regeneration hypertension
- juxtaglomerular index
- © 1971 American Heart Association, Inc.