Haemodynamic and metabolic effects of carbenoxolone in normal subjects and patients with renal impairment.
Carbenoxolone inhibits the enzyme complex 11 beta-hydroxysteroid dehydrogenase. Functional deficiency of this complex might contribute to the hypertension of renal parenchymal disease. We have compared the effects of carbenoxolone (300 mg/day for 5 days) in six normal subjects and seven patients with renal disease. Patients with renal disease had higher blood pressure, plasma creatinine concentration (0.15 +/- 0.01 mmol/L cf. 0.09 +/- 0.01 mmol/L) and urine protein excretion than normals. In normal subjects carbenoxolone increased body weight and plasma chloride and decreased initial urine sodium excretion, packed cell volume, plasma albumin, renin and aldosterone concentrations. In patients with renal disease, carbenoxolone also produced these effects, but in addition significantly increased systolic, (129 +/- 3 to 135 +/- 5 mm Hg) mean (97 +/- 3 to 101 +/- 3 mm Hg) and diastolic blood pressure (81 +/- 3 to 85 +/- 2 mm Hg) and lowered plasma potassium (4.1 +/- 0.1 to 3.8 +/- 0.1 mmol/L) and urine sodium:potassium ratio (1.57 +/- 0.22 to 2.60 +/- 0.54). These results are consistent with the notion that partial deficiency of 11 beta-hydroxysteroid dehydrogenase contributes to the hypertension of renal parenchymal disease.
Whitworth
J A
JA
Department of Medicine and Renal Medicine, St. George Hospital, University of New South Wales, Australia.
Williamson
P M
PM
Brown
M A
MA
Edwards
C R
CR
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000328:Adult; D000450:Aldosterone / Q000097:blood; D001808:Blood Vessels / Q000187:drug effects / Q000502:physiology; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002229:Carbenoxolone / Q000494:pharmacology*; D002712:Chlorides / Q000097:blood; D003404:Creatinine / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000172:deficiency / Q000378:metabolism / Q000502:physiology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D007674:Kidney Diseases / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D011188:Potassium / Q000097:blood; D012083:Renin / Q000097:blood; D012964:Sodium / Q000652:urine
D002712:Chlorides; D000450:Aldosterone; D012964:Sodium; D003404:Creatinine; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases; D012083:Renin; D002229:Carbenoxolone; D011188:Potassium