Anomalous response of urinary kallikrein to deoxycorticosterone in Dahl salt-sensitive rats.
Previous evidence shows that salt-sensitive (S) rats have a net increase in plasma mineralocorticoid activity due to 18-hydroxy-11-deoxycorticosterone and decreased urinary kallikrein excretion compared to salt-resistant (R) rats. Since mineralocorticoids stimulate urinary kallikrein excretion, these results are inconsistent. This inconsistency was explained by the fact that, while R rats responded normally to treatment with deoxycorticosterone (DOC) by an increase in urinary kallikrein excretion, S rats showed no change in urinary kallikrein even when treated with 10 mg of DOC/day for 24 days. S and R rats responded identically to DOC with changes muscle electrolytes and relative hypertrophy of the renal distal tubule. Other measures of chronic mineralocorticoid response in S rats beside kallikrein were, therefore, intact. It was found that S rats were capable of responding to Na deficient diet with an increase in urinary kallikrein comparable to R rats. It was argued, therefore, that mineralocorticoid receptor mechanisms and distal-tubular cell responsiveness are intact in S rats. Mild glomerular and tubular scarring was found in S rats and the severity of renal lesions was increased by DOC treatment in S rats. These lesions correlated well with blood pressure and proteinuria. No such lesions were present in control or DOC treated R rats. It was suggested that failure of urinary kallikrein to respond to DOC in S rats may be a secondary phenomenon resulting from renal damage.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000494:pharmacology*; D004039:Diet, Sodium-Restricted; D004305:Dose-Response Relationship, Drug; D005260:Female; D007610:Kallikreins / Q000652:urine*; D007678:Kidney Glomerulus / Q000187:drug effects; D007686:Kidney Tubules, Distal / Q000187:drug effects; D009132:Muscles / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains / Q000378:metabolism* / Q000502:physiology; D012964:Sodium / Q000378:metabolism
D003900:Desoxycorticosterone; D012964:Sodium; D007610:Kallikreins; D011188:Potassium