Cyclooxygenase-2 contributes to elevated renin in the early postnatal period in rats

Jane Stubbe, Boye L. Jensen, Sebastian Bachmann, Peter Morsing, Ole Skøtt
2003 American Journal of Physiology. Regulatory Integrative and Comparative Physiology  
Cyclooxygenase-2 contributes to elevated renin in the early postnatal period in rats. We asked whether cyclooxygenase (COX) activity controls the renin-angiotensin system in the postnatal period. During kidney development, renin peaked at postnatal days 0-1 at the mRNA, tissue protein [renal renin concentration (RRC)], and plasma renin concentration (PRC) levels and was widely expressed along preglomerular vessels. PRC and renin mRNA expression was elevated until weaning in the 4th postnatal
more » ... he 4th postnatal week compared with adult rats. Renocortical COX-2 was restricted to Tamm-Horsfall protein-positive cells in the thick ascending limb of Henle's loop, and cortical COX-2 mRNA and protein expression were elevated along with PRC in the 2nd and 3rd postnatal weeks. In contrast, cortical COX-1 expression was constant, but medullary COX-1 expression increased eightfold from the 1st to 4th postnatal week. A COX-2-selective blocker, parecoxib, and a nonselective blocker, indomethacin, given in a period with COX-2 induction from postnatal day 6 to day 12, markedly decreased PRC, but not renin mRNA or RRC. Inhibition of angiotensin AT1 receptors by candesartan from postnatal day 1 to day 5 increased COX-2 mRNA (2.5fold), protein, and distribution, renin mRNA (7-fold) and PRC (20-to 70-fold), but had no influence on COX-1 mRNA. Thus, due to very low levels of expression, COX-2 is unlikely to be responsible for the birth peak of renin, but COX-2 activity supports renin secretion later in the suckling period. ANG II negatively feeds back on renocortical COX-2 expression in the 1st postnatal days with high activity of the renin system. We suggest that suckling in the rat is correlated to an enhanced, COX-2-mediated, secretory activity of renin-producing juxtaglomerular cells. candesartan; prostaglandin; parecoxib ANG II has important effects on structural development and functional differentiation of the kidney in the early postnatal life of many species. The key enzyme that initiates ANG I synthesis, renin, is strongly expressed in prenatal and neonatal rodent (12, 18, 28, 43) , sheep (2), and human (33) kidneys, and accordingly there are elevated plasma levels of renin, ANG II, and aldoste-
doi:10.1152/ajpregu.00340.2002 pmid:12560203 fatcat:ljlajftj35b2npdgarjcgiutwa