Aldosterone metabolism in the isolated perfused liver of R and S hypertension-prone Dahl rats.
The effect of a chronic oral salt load on hepatic metabolism of aldosterone was examined in isolated livers of salt-resistant (R) and salt-sensitive (S) hypertension-prone male Dahl rats perfused with d-[4-14C]aldosterone (10(-9) M). Aldosterone was analyzed by radioimmunoassay and [4-14C]aldosterone radiometabolites by high-performance liquid chromatography. In salt-loaded S rats, systolic blood pressure was 30 mmHg higher than in the other three groups (P less than 0.01). In S rats, on standard and high-salt diets, plasma renin activity was 64% (P less than 0.001) and 50% (P less than 0.01) lower, and, on the standard diet, plasma aldosterone was 50% (P less than 0.01) lower than in R rats. Salt loading suppressed plasma renin activity by 42% (P less than 0.05) in R rats and plasma aldosterone by 66 and 33% (P less than 0.01) in R and S rats, respectively. In isolated perfused liver, hepatic function did not differ between various groups. Hepatic clearance of aldosterone in R rats given water and saline and in S rats given water did not differ, whereas hepatic clearance of aldosterone was 28 and 35% higher in salt-loaded S rats when compared with S rats on water (P less than 0.01) and with salt-loaded R rats (P less than 0.001), respectively. Polar and reduced metabolites of [4-14C]aldosterone were released into the circulation in livers of R and S rats on both diets, but highest relative levels of polar metabolites of aldosterone were found in salt-loaded S rats. In all groups, only polar metabolites of aldosterone were excreted in bile.(ABSTRACT TRUNCATED AT 250 WORDS)
Egfjord
M
M
Medical Department P, Rigshospitalet, Copenhagen, Denmark.
Olgaard
K
K
D000450:Aldosterone / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D012965:Sodium Chloride / Q000494:pharmacology*
D012965:Sodium Chloride; D000450:Aldosterone