Upregulation of juxtaglomerular NOS1 and COX-2 precedes glomerulosclerosis in fawn-hooded hypertensive rats.
This study describes elevated histochemical signals for nitric oxide synthase-1 (NOS1) and cyclooxygenase-2 (COX-2) in juxtaglomerular apparatus (JGA) and adjacent thick ascending limb of the kidney of fawn-hooded hypertensive 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 changes in FHH comprised focal segmental glomerulosclerosis (FSGS), focal matrix overexpression, and a moderate arteriolopathy with hypertrophy of the media, enhanced immunoreactivity for alpha-smooth muscle actin, and altered distribution of myofibrils. Macula densa NOS activity, as expressed by NADPH-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), respectively. Even higher elevations were registered for COX-2 immunoreactivity in FHH8 (+166%; P < 0.05) and FHH16 (+157%; P < 0.05). The intensity of renin immunoreactivity and renin mRNA expression in afferent arterioles was also 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 manifestation of glomerulosclerotic damage in FHH. These observations may have implications in understanding the role of local paracrine mediators in glomerular disease.
Weichert
W
W
Anatomisches Institut, Charité, Humboldt Universität, 13353 Berlin, Germany.
Paliege
A
A
Provoost
A P
AP
Bachmann
S
S
D000818:Animals; D051546:Cyclooxygenase 2; D015971:Gene Expression Regulation, Enzymologic; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism* / Q000473:pathology; D006973:Hypertension / Q000378:metabolism* / Q000473:pathology; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D007606:Juxtaglomerular Apparatus / Q000201:enzymology* / Q000473:pathology; D008138:Loop of Henle / Q000201:enzymology / Q000473:pathology; D008297:Male; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase / Q000235:genetics* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D012083:Renin / Q000378:metabolism
D007527:Isoenzymes; D011453:Prostaglandins; D012333:RNA, Messenger; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin