CARBENOXOLONE DOES NOT CAUSE A SYNDROME OF MINERALOCORTICOID EXCESS IN SHEEP

These studies investigated whether treatment with carbenoxolone (CBX), an inhibitor of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD), r esulted in an enhanced mineralocorticoid response to endogenous or inf used cortisol. In conscious sodium replete sheep with a parotid fistul a, infusion of CBX (40 mg/h for 10 days) did not increase mean arteria l pressure, or change sodium and potassium status or plasma renin conc entration, but significantly increased the half-life of 1,2[H-3] corti sol from 18.6 +/- 4.0 to 38.8 +/- 3.9 min (p < 0.05) and reduced the b lood clearance rate of cortisol (BCR) from 31 +/- 3 to 15 +/- 4 L/h (p < 0.01). The reduction in cortisol BCR was associated with reduction in cortisol secretion rate from 433 +/- 116 to 181 +/- 79 nmol/h (p < 0.01). Cortisol (8 mg/h) for 5 days increased mean arterial pressure ( from 83 +/- 2 to 101 +/- 5 mmHg, p < 0.001) and caused natriuresis, hy pokalaemia and hyperglycaemia. These responses were unaltered when cor tisol was infused from the fifth to the tenth day of CBX infusion. The se findings suggest that in sheep, carbenoxolone is either a less pote nt inhibitor of 11 beta-HSD2 than in other species or 11 beta-HSD2 may not be the only mechanism, which determines the specificity of the MR . (C) 1998 by Elsevier Science Inc.