Interactions between 11beta-hydroxysteroid dehydrogenase and COX-2 in kidney.

Yao B, Harris RC, Zhang MZ
Am J Physiol Regul Integr Comp Physiol. 2005 288 (6): R1767-73

PMID: 15718388 · DOI:10.1152/ajpregu.00786.2004

The syndrome of apparent mineralocorticoid excess (SAME) is an autosomal recessive form of salt-sensitive hypertension caused by deficiency of the kidney type 2 11beta-hydroxysteroid dehydrogenase (11betaHSD2). In this disorder, cortisol is not inactivated by 11betaHSD2, occupies mineralocorticoid receptors (MRs), and causes excessive sodium retention and hypertension. In renal medulla, prostaglandins derived from cyclooxygenase-2 (COX-2) stimulate sodium and water excretion, and renal medullary COX-2 expression increases after mineralocorticoid administration. We investigated whether medullary COX-2 also increases in rats with 11betaHSD2 inhibition and examined its possible role in the development of hypertension. 11betaHSD2 inhibition increased medullary and decreased cortical COX-2 expression in adult rats and induced high blood pressure in high-salt-treated rats. COX-2 inhibition had no effect on blood pressure in control animals but further increased blood pressure in high-salt-treated rats with 11betaHSD2 inhibition. COX-1 inhibition had no effect on blood pressure in either control or experimental animals. 11betaHSD2 inhibition also led to medullary COX-2 increase and cortical COX-2 decrease in weaning rats, primarily through activation of MRs. In the suckling rats, medullary COX-2 expression was very low, consistent with a urinary concentrating defect. 11betaHSD2 inhibition had no effect on either cortical or medullary COX-2 expression in the suckling rats, consistent with low levels of circulating corticosterone in these animals. These data indicate that COX-2 plays a modulating role in the development of hypertension due to 11betaHSD2 deficiency and that 11betaHSD2 regulates renal COX-2 expression by preventing glucocorticoid access to MRs during postnatal development.

MeSH Terms (21)

17-Hydroxysteroid Dehydrogenases Animals Animals, Newborn Animals, Suckling Blood Pressure Cyclooxygenase 2 Enzyme Inhibitors Female Glycyrrhizic Acid Hormone Antagonists Hypertension Immunoblotting Immunohistochemistry Kidney Kidney Cortex Kidney Medulla Mifepristone Pregnancy Prostaglandin-Endoperoxide Synthases Rats Rats, Sprague-Dawley

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