Overexpression of inducible nitric oxide synthase in the kidney of the spontaneously hypertensive rat.
In kidney, nitric oxide (NO) produced by nitric oxide synthase (NOS) regulates sodium and water excretion and renal medullary blood flow. However, excessive NO production causes nitrative damage and oxidative stress. Since oxidative stress may be linked to hypertension, we examined the expression and activity of inducible NOS (iNOS) in the kidney of the spontaneously hypertensive rat (SHR) and compared our findings to control normtotensive Wistar Kyoto (WKY) rat. Compared with WKY rat, there was significant (p < .05) overexpression (by 96%) and increased (2-fold) activity of iNOS in the cortex but not in the outer medulla, of SHR kidney; in the inner medulla, there was a 6.9-fold increase in iNOS activity in SHR. Increased expression (by 104%) and activity (3.3-fold) of iNOS was specifically observed in proximal tubules (PTs) of the cortex, accompanied by higher (2-fold) tissue nitrite levels. Although certain antioxidant enzymes such as catalase and Mn-superoxide dismutase were overexpressed, glutathione peroxidase was underexpressed in SHR PTs. Overexpression of the inducer of the iNOS promoter, nuclear factor-kappaB (NF-kappaB), with elevated nitrotyrosinylated proteins, further confirmed an elevated state of iNOS-induced oxidative stress in SHR kidneys, possibly signifying its role in the maintenance of essential hypertension seen in these animals.
Kumar
Ujendra
U
Fraser Laboratories for Diabetes Research, Royal Victoria Hospital, Montreal, Canada.
Chen
Jun
J
Sapoznikhov
Valeriy
V
Canteros
Griselda
G
White
Beatrix H
BH
Sidhu
Anita
A
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D006977:Hypertension, Renal / Q000378:metabolism*; D007150:Immunohistochemistry; D007687:Kidney Tubules, Proximal / Q000201:enzymology*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II; D018384:Oxidative Stress / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000378:metabolism
D000975:Antioxidants; D016328:NF-kappa B; C002744:3-nitrotyrosine; D014443:Tyrosine; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat