1 Det Sundhedsvidenskabelige Fakultet, SDU2 Nephrology, Department of Clinical Research, Det Sundhedsvidenskabelige Fakultet, SDU3 Kardiovaskulær og Renal Forskning, Department of Molecular Medicine, Det Sundhedsvidenskabelige Fakultet, SDU4 Dean, Faculty of Health Sciences, Faculty Secretariat, Det Sundhedsvidenskabelige Fakultet, SDU5 unknown6 Kardiovaskulær og Renal Forskning, Department of Molecular Medicine, Det Sundhedsvidenskabelige Fakultet, SDU7 Dean, Faculty of Health Sciences, Faculty Secretariat, Det Sundhedsvidenskabelige Fakultet, SDU
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 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 AT(1) receptors by candesartan from postnatal day 1 to day 5 increased COX-2 mRNA (2.5-fold), 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.
American Journal of Physiology: Regulatory, Integrative and Comparative Physiology, 2003, Vol 284, Issue 5