Altered expression of prostacyclin synthase in a subset of the thick ascending limb cells and mesangial cells in 5/6-nephrectomized rats.
The aim of this study was to evaluate the possible role of prostacyclin (PGl2) in the onset and development of hypertension and chronic renal failure in 5/6-nephrectomized rats (5/6NX). We measured the systolic blood pressure, 24-h urinary excretion levels of 6-keto-PGF1alpha, which was a stable metabolite of PGI2, and levels of PGI2 synthase (PCS) mRNA in the kidneys. Immunostaining for PCS in the kidneys was also evaluated. Systolic blood pressure was higher in 5/6NX than in sham-operated rats. The 24-h urinary excretion levels of 6-keto-PGF1alpha in 5/6NX at 1 week postsurgery were lower than in sham-operated rats. In renal morphology, tubulointerstitial injury was observed at 2 weeks postsurgery, and glomerulosclerosis at 4 weeks. Levels of PCS mRNA in 5/6NX decreased significantly at 1 and 2 weeks postsurgery compared with those in sham-operated rats, but at 8 weeks these levels showed a tendency to increase. Immunostaining for PCS was positive in a subset of the cortical thick ascending limb of Henle's loop cells, including macula densa in both groups. Moreover, in 5/6NX at 8 weeks postsurgery, mesangial cells also stained positive for PCS. In conclusion, our findings suggest that PCS might play an important role in mitigating glomerular hemodynamic changes associated with reduction of renal mass.
Tomida
T
T
Internal Medicine II, Nagoya University School of Medicine, Japan. tomida@med.nagoya-u.ac.jp
Numaguchi
Y
Y
Matsui
H
H
Toki
Y
Y
Ito
T
T
Okumura
K
K
Hayakawa
T
T
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D001794:Blood Pressure; D002940:Circadian Rhythm; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D005920:Glomerular Mesangium / Q000201:enzymology* / Q000473:pathology; D006321:Heart / Q000503:physiopathology; D006339:Heart Rate; D006728:Hormones / Q000097:blood; D007150:Immunohistochemistry; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D008138:Loop of Henle / Q000201:enzymology* / Q000473:pathology; D008297:Male; D009392:Nephrectomy / Q000379:methods*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013599:Systole; D013929:Thromboxane B2 / Q000652:urine
D006728:Hormones; D012333:RNA, Messenger; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D003577:Cytochrome P-450 Enzyme System; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase