Acute reduction of renal 11 beta-hydroxysteroid dehydrogenase activity by several antinatriuretic stimuli.
The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) activity of the kidney prevents access of cortisol or corticosterone to the renal mineralocorticoid receptor. Reduction of 11 beta-HSD activity by nutritional, hormonal, or pharmacologic factors might enhance the mineralocorticoid effect of these corticosteroids, thus causing sodium retention. To test this concept, we studied the effect on 11 beta-HSD activity of several antinatriuretic factors given orally to rats or exposed in vitro to rat renal tissue. Renal 11 beta-HSD activity was higher in fasted than fed rats (P < .05). Glucose, ethanol, and Toradol (Syntex Laboratories, Palo Alto, CA) given orally to fasted rats all reduced renal 11 beta-HSD activity by 20% to 40% (P < .05-.005) to levels similar to those observed in fed animals. Incubation of renal tissue from fasted rats with physiologic concentrations of insulin, ethanol, and Toradol also reduced 11 beta-HSD activity by 20% to 40% (P < .05-.01). These findings are consistent with the hypothesis that the antinatriuretic actions of these stimuli are due in part to alteration of renal 11 beta-HSD leading to greater mineralocorticoid effects in kidney.
Riddle
M C
MC
Department of Medicine, Oregon Health Sciences University, Portland 97201-3098.
McDaniel
P A
PA
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000284:Administration, Oral; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D003345:Corticosterone / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004435:Eating / Q000502:physiology; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005215:Fasting / Q000378:metabolism / Q000502:physiology; D005947:Glucose / Q000008:administration & dosage / Q000494:pharmacology*; D006854:Hydrocortisone / Q000378:metabolism; D006913:Hydroxysteroid Dehydrogenases / Q000032:analysis* / Q000378:metabolism / Q000502:physiology; D007328:Insulin / Q000494:pharmacology; D020911:Ketorolac Tromethamine; D007668:Kidney / Q000201:enzymology*; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014046:Tolmetin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014325:Tromethamine / Q000008:administration & dosage / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D007328:Insulin; D014325:Tromethamine; D000431:Ethanol; D020911:Ketorolac Tromethamine; D014046:Tolmetin; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D005947:Glucose; D003345:Corticosterone; D006854:Hydrocortisone