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Interactions between 11β-hydroxysteroid dehydrogenase and COX-2 in kidney
- Source :
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 288:R1767-R1773
- Publication Year :
- 2005
- Publisher :
- American Physiological Society, 2005.
-
Abstract
- 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.
- Subjects :
- medicine.medical_specialty
Kidney Cortex
17-Hydroxysteroid Dehydrogenases
Physiology
medicine.drug_class
Immunoblotting
Blood Pressure
Dehydrogenase
Biology
Kidney
Rats, Sprague-Dawley
chemistry.chemical_compound
Hormone Antagonists
Mineralocorticoid receptor
Pregnancy
Corticosterone
Physiology (medical)
Internal medicine
Renal medulla
medicine
Animals
Enzyme Inhibitors
Hydrocortisone
Kidney Medulla
Glycyrrhizic Acid
Immunohistochemistry
Animals, Suckling
Rats
Mifepristone
medicine.anatomical_structure
Endocrinology
Animals, Newborn
chemistry
Cyclooxygenase 2
Prostaglandin-Endoperoxide Synthases
Mineralocorticoid
Hypertension
Female
Glucocorticoid
medicine.drug
Subjects
Details
- ISSN :
- 15221490 and 03636119
- Volume :
- 288
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Regulatory, Integrative and Comparative Physiology
- Accession number :
- edsair.doi.dedup.....e3bd22b172c451637be146fec237565e