Upregulation of juxtaglomerular NOS1 and COX-2 precedes glomerulosclerosisin fawn-hooded hypertensive rats

Citation
W. Weichert et al., Upregulation of juxtaglomerular NOS1 and COX-2 precedes glomerulosclerosisin fawn-hooded hypertensive rats, AM J P-REN, 280(4), 2001, pp. F706-F714
Citations number
44
Language
INGLESE
art.tipo
Article
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
ISSN journal
0363-6127 → ACNP
Volume
280
Issue
4
Year of publication
2001
Pages
F706 - F714
Database
ISI
SICI code
0363-6127(200104)280:4<F706:UOJNAC>2.0.ZU;2-1
Abstract
This study describes elevated histochemical signals for nitric oxide syntha se-1 (NOS1) and cyclooxygenase-2 (COX-2) in juxtaglomerular apparatus (JGA) and adjacent thick ascending limb of the kidney of fawn-hooded hypertensiv e rats (FHH). Two different age groups of FHH (8 and 16 wk; FHH8 and FHH16, respectively) were compared with genetically related fawn-hooded rats with normal blood pressure (FHL) that served as controls. Histopathological cha nges in FHH comprised focal segmental glomerulosclerosis (FSGS), focal matr ix overexpression, and a moderate arteriolopathy with hypertrophy of the me dia, enhanced immunoreactivity for alpha -smooth muscle actin, and altered distribution of myofibrils. Macula densa NOS activity, as expressed by NADP H-diaphorase staining, and NOS1 mRNA abundance were significantly elevated in FHH8 (+153 and +88%; P < 0.05) and FHH16 (+93 and +98%; P < 0.05), respe ctively. Even higher elevations were registered for COX-2 immunoreactivity in FHH8 (+166%; P < 0.05) and FHH16 (+157%; P < 0.05). The intensity of ren in immunoreactivity and renin mRNA expression in afferent arterioles was al so elevated in FHH8 (+51 and +166%; P < 0.05) and FHH16 (+105 and +136%; P < 0.05), respectively. Thus we show that coordinate upregulation of tubular NOS1, COX-2, and renin expression precedes, and continues after, the manif estation of glomerulosclerotic damage in FHH. These observations may have i mplications in understanding the role of local paracrine mediators in glome rular disease.