title: 19-Nordeoxycorticosterone excretion in male and female inbred salt-sensitive (S/JR) and salt-resistant (R/JR) Dahl rats.
abstract: Rats were selectively bred for susceptibility (S) and resistance (R) to the hypertensinogenic effects of excess salt intake by Dahl and further inbred to virtual homozygosity by Rapp (S/JR and R/JR). The S strain has been shown to have a mutation of the cytochrome P-450-dependent 11 beta,18-hydroxylase resulting in the enhanced production of 18-hydroxydeoxycorticosterone (18-OH-DOC) compared to that of the R strain. It is known that this enzyme is also responsible for the hydroxylation of deoxycorticosterone at the 19 position to produce 19-hydroxydeoxycorticosterone. Recently, the excretion of 19-nordeoxycorticosterone (19-nor-DOC), a potent mineralocorticoid, has been shown to be markedly increased in S/JR females compared to that in R/JR females consuming a high sodium diet. While the S/JR rat is spontaneously hypertensive, the course of the disease is greatly accelerated and exacerbated by a high sodium diet. If, indeed, 19-nor-DOC is responsible for the spontaneous hypertension in the S/JR rat, then its production should also be higher in the S/JR rat consuming a normal salt diet. Furthermore, since its production is suppressed by NaCl intake, the excretion should be even higher when not suppressed by a high sodium diet. We measured the urinary excretion of 19-nor-DOC, 18-OH-DOC, and corticosterone in male and female S/JR and R/JR rats consuming a normal sodium diet. The excretions of corticosterone and 18-OH-DOC were significantly higher by S/JR of both sexes than by R/JR, with the excretion by female rats being higher than that by male rats within the same strain. The hierarchy of excretion rates of 19-nor-DOC was: S/JR females greater than R/JR females greater than S/JR males greater than R/JR male rats. These studies indicate that while S/JR rats of both sexes develop higher blood pressures than the R/JR even on a standard salt intake, the excretion of 19-nor-DOC does not correlate well with their blood pressure elevation, since the normotensive female R/JR rat excretes significantly higher quantities of 19-nor-DOC than the hypertensive male S/JR rat. Thus, it is unclear whether 19-nor-DOC is playing a significant role in the pathogenesis of the hypertension in the S/JR rat. It also remains unknown whether the renal site of formation of 19-nor-DOC allows access to the mineralocorticoid target sites in the kidney.
authors.affiliation: Research Service, James A. Haley Veterans Administration Medical Center, Tampa, Florida 33612.
authors.forename: E P
authors.initials: EP
authors.lastname: Gomez-Sanchez
authors.forename: C E
authors.initials: CE
authors.lastname: Gomez-Sanchez
mesh_terms: D000818:Animals; D001794:Blood Pressure; D003345:Corticosterone / Q000652:urine; D003900:Desoxycorticosterone / Q000031:analogs & derivatives* / Q000652:urine; D005260:Female; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics / Q000652:urine*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D012727:Sex Characteristics; D012982:Sodium, Dietary / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D012982:Sodium, Dietary; C042509:18-hydroxydeoxycorticosterone; D003900:Desoxycorticosterone; C019026:19-nordeoxycorticosterone; D003345:Corticosterone