Immunohistochemically detected protein nitration indicates sites of renal nitric oxide release in Goldblatt hypertension.
In the kidney, nitric oxide (NO) from the macula densa (MD) is considered an integral modulator of the tubulovascular message system, whereas endothelium-derived NO is a major vasorelaxing factor. The goal of the present study was to determine extracellular pathways of NO in rats with renovascular two-kidney, one clip Goldblatt hypertension (2K1C). To localize NO in the tissue, immunohistochemical detection of NO-dependent tyrosine nitration was performed using a monoclonal antibody against nitrotyrosine. Nitration of phenolic compounds such as tyrosine results from the reaction with peroxynitrite (ONOO ) formed by NO and molecular oxygen or superoxide and may therefore be used as a footprint for local release of NO. Significant nitrotyrosine immunoreactivity was detected in the extraglomerular mesangium (EGM) of the stenotic kidney in 2K1C rats, whereas in the nonclipped contralateral kidney and in control animals no signal was detected at this site. Positive staining of the EGM was paralleled by enhanced NADPH diaphorase (NADPH-d) staining of the adjacent MD, signifying increased type I nitric oxide synthase (NOS) activity in the stenotic kidney. In contrast, in the cortical vasculature selectively enhanced nitrotyrosine immunoreactivity was detected in the arteriolar wall of the nonclipped contralateral kidney, and endothelial NADPH-d signal, indicating NOS Type III activity, was enhanced in parallel. Our results suggest that in MD, stimulation of NOS in the stenotic Goldblatt kidney induces the release of NO into the EGM. From there an NO-dependent intermediate stimulus may reach the glomerular vasculature. Footprints of NO-dependent effects in the vascular smooth muscle layer of the non-clipped contralateral kidney indicate a marked vasodilatory response that may have been caused by enhanced shear stress and/or angiotensin II levels.
Bosse
H M
HM
Department of Anatomy, University of Heidelberg, Germany.
Bachmann
S
S
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism; D006978:Hypertension, Renovascular / Q000378:metabolism*; D007150:Immunohistochemistry; D007606:Juxtaglomerular Apparatus / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D009566:Nitrates / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation; D014018:Tissue Distribution; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism*
D009566:Nitrates; D009569:Nitric Oxide; C002744:3-nitrotyrosine; D014443:Tyrosine