Possible role of 18-hydroxy-deoxycorticosterone in hypertension.

Abstract

OUR studies on two strains of rats with opposite genetic predisposition to hypertension showed that their adrenal steroid production differed significantly1,2. This suggested a theory concerning the role of mineralocorticoids in the initiation of hypertension. The two strains of rats3–9 were separated genetically on the basis of their disparate blood pressure responses to salt (NaCl). The members of one strain (sensitive or S) rapidly develop fatal hypertension from salt intakes to which members of the other strain (resistant or R) respond only mildly, if at all. These same effects were shown when five other techniques were used to induce experimental hypertension (deoxycorticosterone acetate plus NaCl; unilateral renal artery compression without NaCl; cortisone without NaCl; adrenal regeneration with NaCl; uninephrectomy without (or with—unpublished observations) NaCl). Since the genetic influence seems critical in determining the effectiveness of a variety of stimuli known to induce experimental hypertension, we have suggested that a similar situation prevails in human hypertension6,9. Breeding experiments have shown that the control of these dramatic blood pressure differences between S and R rats is due to the expressions of two to four genes8. Our objective was to identify the biochemical mechanism controlled by each gene.