Premium
Pathogenetic role of cyclooxygenase‐2 in hyperprostaglandin E syndrome/antenatal bartter syndrome: Therapeutic use of the cyclooxygenase‐2 inhibitor nimesulide
Author(s) -
Nüsing Rolf M.,
Reinalter Stephan C.,
Peters Melanie,
Kömhoff Martin,
Seyberth Hannsjörg W.
Publication year - 2001
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(01)21861-x
Subject(s) - medicine , bartter syndrome , hypercalciuria , hyperaldosteronism , nephrocalcinosis , endocrinology , polyuria , nimesulide , cyclooxygenase , bartter's syndrome , kidney , aldosterone , urinary system , hypokalemia , chemistry , enzyme , diabetes mellitus , biochemistry
Patients with hyperprostaglandin E syndrome/antenatal Bartter syndrome typically have renal salt wasting, hypercalciuria with nephrocalcinosis, and secondary hyperaldosteronism. Antenatally, these patients have fetal polyuria, leading to polyhydramnios and premature birth. Hyperprostaglandin E syndrome/antenatal Bartter syndrome is accompanied by a pathologically elevated synthesis of prostaglandin E 2 , thought to be responsible for aggravation of clinical symptoms such as salt and water loss, vomiting, diarrhea, and failure to thrive. In this study administration of the cyclooxygenase‐2 (COX‐2) specific inhibitor nimesulide to patients with hyperprostaglandin E syndrome/antenatal Bartter syndrome blocked renal prostaglandin E 2 formation and relieved the key parameters hyperprostaglandinuria, secondary hyperaldosteronism, and hypercalciuria. Partial suppression of serum thromboxane B 2 synthesis resulting from platelet COX‐1 activity and complete inhibition of urinary 6‐keto‐prostaglandin F 1α , reflecting endothelial COX‐2 activity, indicate preferential inhibition of COX‐2 by nimesulide. Amelioration of the clinical symptoms by use of nimesulide indicates that COX‐2 may play an important pathogenetic role in hyperprostaglandin E syndrome/antenatal Bartter syndrome. Moreover, on the basis of our data we postulate that COX‐2‐derived prostaglandin E 2 is an important mediator for stimulation of the renin‐angiotensin‐aldosterone system in the kidney. Clinical Pharmacology & Therapeutics (2001) 70 , 384–390; doi: 10.1016/S0009‐9236(01)21861‐X