Regulation and function of renal medullary cyclooxygenase-2 during high salt loading.
Prostaglandins (PGs) are important autocrine/paracrine regulators that contribute to sodium balance and blood pressure control. Along the nephron, the highest amount of PGE2is found in the distal nephron, an important site for fine-tuning of urinary sodium and water excretion. Cylooxygenase-2 (COX-2) is abundantly expressed in the renal medulla and its expression along with urinary PGE2excretion is highly induced by chronic salt loading. Factors involved in high salt-induced COX-2 expression in the renal medulla include the hypertonicity, fluid shear stress (FSS), and hypoxia-inducible factor-1 alpha (HIF-1 alpha). Site-specific inhibition of COX-2 in the renal medulla of Sprague-Dawley rats causes sodium retention and salt-sensitive hypertension. Together, these results support the concept that renal medullary COX-2 functions an important natriuretic mediator that is activated by salt loading and its products promote sodium excretion and contribute to maintenance of sodium balance and blood pressure.
Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah, Tianxin.Yang@hsc.utah.edu.
Tianxin
T
Yang
Department of Internal Medicine, University of Utah and Veterans Affairs Medical Center, Salt Lake City, Utah and Institute of Hypertension, Sun Yat-sen University School of Medicine, Guangzhou, 510080, China.
Mi
M
Liu
D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D006973:Hypertension / Q000209:etiology / Q000378:metabolism; D007679:Kidney Medulla / Q000201:enzymology*; D009318:Natriuresis; D051381:Rats; D015398:Signal Transduction; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage*
D017673:Sodium Chloride, Dietary; D051546:Cyclooxygenase 2; D015232:Dinoprostone