Effects of Glycyrrhizin on Production of Vascular Aldosterone and Corticosterone

This study is to confirm the role of glycyrrhizin on blood pressure and to test the effects of glycyrrhizin on production of vascular aldosterone and corticosterone in rats. Male Wistar rats received glycyrrhizin (Sigma) 200 mg/kg/day p.o. for 5 weeks, and blood pressure was monitored by a pressure transducer. Systolic blood pressure significantly increased in Wistar rats treated with glycyrrhizin compared to that without glycyrrhizin. Mesenteric artery perfusion ex vivo and pressor responses to norepinephrine were performed. The pressor responses to norepinephrine in mesenteric arteries treated with glycyrrhizin were significantly increased. The perfusate from the mesenteric arteries was collected and applied to a Sep-Pak C 18 cartridge column, used for reverse-phase high-performance liquid chromatography, and measured for both aldosterone and corticosterone by radioimmunoassay. Levels of aldosterone were decreased but those of corticosterone increased in perfusate from arteries treated with glycyrrhizin. RT-PCR showed that glycyrrhizin inhibited the expression of 11β- HSD2 and CYP11B2 mRNA in mesenteric arteries. These results confirm that glycyrrhizin is able to induce hypertension, and provide evidence that it inhibits the transcriptions of both 11β-HSD2 and CYP11B2 in the vasculature, leading to lower aldosterone and higher corticosterone production in vessels, and increased vasoconstrictor responses to norepinephrine.

[1]  T. Mune,et al.  11 beta-Hydroxysteroid dehydrogenase and its role in the syndrome of apparent mineralocorticoid excess. , 2001, Pediatric research.

[2]  J. Challis,et al.  [11 beta-Hydroxysteroid dehydrogenase]. , 1998, Sheng li ke xue jin zhan [Progress in physiology].

[3]  Z. Krozowski.  The 11β-Hydroxysteroid dehydrogenase enzymes: perspectives and paradoxes. , 1996 .

[4]  H. Raff,et al.  Differentiation of the expression of aldosterone synthase and 11β-hydroxylase mRNA in the rat adrenal cortex by reverse transcriptase-polymerase chain reaction , 1995, The Journal of Steroid Biochemistry and Molecular Biology.

[5]  C. Gomez-Sanchez,et al.  Cloning, expression, and tissue distribution of the rat nicotinamide adenine dinucleotide-dependent 11 beta-hydroxysteroid dehydrogenase. , 1995, Endocrinology.

[6]  Hiroshi Yamamoto,et al.  Aldosterone biosynthesis and action in vascular cells , 1995, Steroids.

[7]  P. Stewart,et al.  7 11-hydroxysteroid dehydrogenase , 1994 .

[8]  P. White,et al.  Genetic analysis of 11β-hydroxysteroid dehydrogenase , 1994, Steroids.

[9]  M. Schambelan.  Licorice ingestion and blood pressure regulating hormones , 1994, Steroids.

[10]  B. Walker,et al.  Deficient inactivation of cortisol by 11β‐hydroxysteroid dehydrogenase in essential hypertension , 1993, Clinical endocrinology.

[11]  J. Nishimura,et al.  cAMP induces up-regulation of ETA receptor mRNA and increases responsiveness to endothelin-1 of rat aortic smooth muscle cells in primary culture. , 1992, Biochemical and biophysical research communications.

[12]  J. Funder,et al.  Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. , 1988, Science.

[13]  T. Mune,et al.  11β-Hydroxysteroid Dehydrogenase and Its Role in the Syndrome of Apparent Mineralocorticoid Excess , 1997, Pediatric Research.

[14]  Z. Krozowski.  The 11 beta-hydroxysteroid dehydrogenase enzymes: perspectives and paradoxes. , 1996, Endocrine research.

[15]  C. Edwards,et al.  Localisation of 11 beta-hydroxysteroid dehydrogenase--tissue specific protector of the mineralocorticoid receptor. , 1988, Lancet.

[16]  I. Miyamori,et al.  Participation of vascular prostacyclin for the pathogenesis of experimental glucocorticoid hypertension in rats. , 1985, Clinical and experimental hypertension. Part A, Theory and practice.