Electrolyte Blood Press.  2007 Dec;5(2):89-94. 10.5049/EBP.2007.5.2.89.

Altered Regulation of 11beta-hydroxysteroid Dehydrogenase II in the Kidney of Rats with Experimental Hypertension

• Kang SS
• Kim SW
• Lee JU

• KMID: 2052290
• DOI: http://doi.org/10.5049/EBP.2007.5.2.89

Abstract

The present study was aimed at investigating the role of type II 11beta-hydroxysteroid dehydrogenase (IIbeta- HSD II) in the development of hypertension. Two-kidney, one-clip (2K1C), deoxycorticosterone acetate (DOCA)/salt, or NG-nitro-L-arginine methyl ester (L-NAME) hypertension was induced in male Sprague- Dawley rats. Four weeks later, the expression of 11beta-HSD II mRNA was determined in the kidney by Northern blot analysis. The plasma level of aldosterone was measured by radioimmunoassay. In 2K1C hypertension, the expression of 11beta-HSD II was decreased in the clipped kidney and increased in the non-clipped kidney. The expression was increased in the remnant kidney of DOCA/salt hypertension, while decreased in the kidneys of L-NAME hypertension. The plasma level of aldosterone was increased, decreased, and remained unchanged in 2K1C, DOCA/salt, and L-NAME hypertension, respectively. The down-regulation of 11beta-HSD II may contribute to the sodium retention, thereby increasing the blood pressure in 2K1C and L-NAME hypertension. On the contrary, the up-regulation in DOCA/salt hypertension may play a compensatory role to dissipate the sodium retention.

MeSH Terms

11-beta-Hydroxysteroid Dehydrogenases*
Aldosterone
Animals
Blood Pressure
Blotting, Northern
Desoxycorticosterone
Down-Regulation
Humans
Hypertension*
Kidney*
Male
NG-Nitroarginine Methyl Ester
Plasma
Radioimmunoassay
Rats*
RNA, Messenger
Sodium
Up-Regulation
11-beta-Hydroxysteroid Dehydrogenases
Aldosterone
Desoxycorticosterone
NG-Nitroarginine Methyl Ester
RNA, Messenger
Sodium

Figure

• 

  Fig. 1 Representative Northern blot autoradiograms and densitometric data showing type II 11β-hydroxysteroid dehydrogenase (11β-HSD II) mRNA in the clipped kidney of two-kidney, one-clip rats. The open column represents the control and the hatched column depicts the hypertensive group (mean±SEM of 4 experiments each). *p<0.05, compared with control.

• 

  Fig. 2 Representative Northern blot autoradiograms and densitometric data showing 11β-HSD II mRNA in the non-clipped kidney of two-kidney, one-clip rats. The open column represents the control and the hatched column depicts the hypertensive group (mean±SEM of 4 experiments each). *p<0.05 compared with control.

• 

  Fig. 3 Representative Northern blot autoradiograms and densitometric data showing type II 11β-hydroxysteroid dehydrogenase (11β-HSD II) mRNA in the remnant kidney of deoxycorticosterone acetate (DOCA)/salt hypertension.. The open column represents the control and the hatched column depicts the hypertensive group (mean±SEM of 4 experiments each). *p<0.05 compared with control.

• 

  Fig. 4 Representative Northern blot autoradiograms and densitometric data showing type II 11β-hydroxysteroid dehydrogenase (11β-HSD II) mRNA in the kidney of NGnitro-L-arginine methyl ester (L-NAME) induced hypertension.. The open column represents the control and the hatched column depicts the hypertensive group (mean±SEM of 4 experiments each). *p<0.05 compared with control.

Reference

1. Eaton DC, Becchetti A, Ma H, Ling BN. Renal sodium channels: regulation and single channel properties. Kidney Int. 1995; 48:941–949. PMID: 8569103.

2. Renard S, Voilley N, Bassilana F, Lazdunski M, Barbry P. Localization and regulation by steroids of the alpha, beta and gamma subunits of the amiloride-sensitive Na⁺ channel in colon, lung and kidney. Pflugers Arch. 1995; 430:299–307. PMID: 7491252.

3. Funder JW, Pearce PT, Smith R, Smith AI. Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated. Science. 1988; 242:583–585. PMID: 2845584.

4. Edwards CRW, Stewart PM, Burt D, Brett L, McIntyre MA, Sutanto WS, DeKloet ER, Monder C. Localization of 11β-hydroxysteroid dehydrogenase-tissue specific protector of the mineralocorticoid receptor. Lancet. 1988; 2:986–989. PMID: 2902493.

5. Rundle SE, Funder JW, Lakshmi V, Monder C. The intrarenal localization of mineralocorticoid receptors and 11β-dehydrogenase: immunocytochemical studies. Endocrinology. 1989; 125:1700–1704. PMID: 2547593.

6. Bailey MA, Unwin RJ, Shirley DG. In vivo inhibition of renal 11beta-hydroxysteroid dehydrogenase in the rat stimulates collecting duct sodium reabsorption. Clin Sci(Lond). 2001; 101:195–198. PMID: 11473496.

7. Wilson RC, Krozowski ZS, Li K, Obeyesekere VR, Razzaghy-Azar M, Harbison MD, Wei JQ, Shackleton CH, Funder JW, New MI. A mutation in the HSD11β2 gene in a family with apparent mineralocorticoid excess. J Clin Endocrinol Metab. 1995; 80:2263–2266. PMID: 7608290.

8. Kotelevtsev Y, Brown RW, Fleming S, Kenyon C, Edwards CR, Seckl JR, Mullins JJ. Hypertension in mice lacking 11beta-hydroxysteroid dehydrogenase type 2. J Clin Invest. 1999; 103:683–689. PMID: 10074485.

9. Walker BR, Stewart PM, Shackleton CHL, Padfield PL, Edwards CRW. Deficient inactivation of cortisol by 11 beta-hydroxysteroid dehydrogenase in essential hypertention. Clin Endocrinol(Oxf). 1993; 39:221–227. PMID: 8370136.

10. Stewart PM, Valentino R, Wallance AM, Burt D, Shackleton CHL, Edwards CRW. Mineralocorticoid activity of liquorice: 11β-hydroxysteroid dehydrogenase deficiency comes to age. Lancet. 1987; 2:821–824. PMID: 2889032.

11. Farese RV Jr, Biglieri EG, Shackleton CH, Irony I, Gomez-Fontes R. Licorice-induced hypermineralocorticoidism. N Engl J Med. 1991; 325:1223–1227. PMID: 1922210.

12. Pohlova I, Miksik I, Kunes J, Pacha J. 11beta-hydroxysteroid dehydrogenase activity in spontaneously hypertensive and Dahl rats. Am J Hypertens. 2000; 13:927–933. PMID: 10950402.

13. Hermans JJ, Steckel B, Thijssen HH, Janssen BJ, Netter KJ, Maser E. Comparison of 11 beta-hydroxysteroid dehydrogenase in spontaneously hypertensive and Wistar-Kyoto rats. Steroids. 1995; 60:773–779. PMID: 8585102.

14. Chomczynski P, Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987; 162:156–159. PMID: 2440339.

15. Zhou M-Y, Gomez-Sanchez EP, Cox DL, Cosby D, Gomez-Sanchez CE. Cloning, expression, and tissue distribution of the rat nicotinamide adenine dinucleotide-dependent 11β-hydroxysteroid dehydrogenase. Endocrinology. 1995; 136:3729–3734. PMID: 7649078.

16. Takeda Y, Inba S, Furukawa K, Miyamori I. Renal 11β-hydroxysteroid dehydrogenase in genetically saltsensitive hypertensive rats. Hypertension. 1998; 32:1077–1082. PMID: 9856977.

17. Lloyd-MacGilp SA, Nelson SM, Florin M, Lo M, McKinnell J, Sassard J, Kenyon CJ. 11β-hydroxysteroid dehydrogenase and corticosteroid action in Lyon hypertensive rats. Hypertension. 1999; 34:1123–1128. PMID: 10567193.

18. Escher G, Vogt B, Beck T, Guntern D, Frey BM, Frey FJ. Reduced 11beta-hydroxysteroid dehydrogenase activity in the remaining kidney following nephrectomy. Endocrinology. 1998; 139:1533–1539. PMID: 9528931.

19. Alfaidy N, Blot-Chabaud M, Bonvalet JP, Farman N. Vasopressin potentiates mineralocorticoid selectivity by stimulating 11 beta hydroxysteroid dehydrogenase in rat collecting duct. J Clin Invest. 1997; 100:2437–2442. PMID: 9366557.

20. Ricketts ML, Stewart PM. Regulation of 11beta-hydroxysteroid dehydrogenase type 2 by diuretics and the renin-angiotensin-aldosterone axis. Clin Sci(Lond). 1999; 96:669–675. PMID: 10334975.

21. Giordano M, Vermeulen EM, Trevani AS, Dran G, Andonegui G, Geffner JR. Nitric oxide synthase inhibitors enhance plasma levels of corticosterone and ACTH. Acta Physiol Scand. 1996; 157:259–264. PMID: 8800367.

22. Hatakeyama H, Inaba S, Taniguchi N, Miyamori I. Functional adrenocorticotropic hormone receptor in cultured human vascular endothelial cells: possible role in control of blood pressure. Hypertension. 2000; 36:862–865. PMID: 11082157.

23. Lou YK, Wen C, Li M, Adams DJ, Wang MX, Yang F, Morris BJ, Whitworth JA. Decreased renal expression of nitric oxide synthase isoforms in adrenocorticotropin-induced and corticosterone-induced hypertension. Hypertension. 2001; 37:1164–1170. PMID: 11304519.

24. Stoos BA, Garcia NH, Garvin JL. Nitric oxide inhibits sodium reabsorption in the isolated perfused cortical collecting duct. J Am Soc Nephrol. 1995; 6:89–94. PMID: 7579075.