Nitric oxide generated by nNOS in the macula densa regulates the afferent arteriolar diameter in rat kidney

2004 ◽  
Vol 37 (4) ◽  
pp. 236-241 ◽  
Author(s):  
Akihiro Tojo ◽  
Maristela Lika Onozato ◽  
Satoru Fukuda ◽  
Kensuke Asaba ◽  
Kenjiro Kimura ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Rat Kidney ◽  
Macula Densa ◽  
Arteriolar Diameter

Selective neuronal nitric oxide synthase inhibition blocks furosemide-stimulated renin secretion in vivo

1995 ◽  
Vol 269 (1) ◽  
pp. F134-F139 ◽  
Author(s):  
W. H. Beierwaltes
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Nitric Oxide Synthase ◽  
Perfusion Pressure ◽  
Renal Perfusion ◽  
Macula Densa ◽  
Renin Secretion ◽  
Renal Perfusion Pressure ◽  
Neuronal Nos ◽  
Oxide Synthase

The macula densa is a regulatory site for renin. It contains exclusively the neuronal isoform of nitric oxide synthase (NOS), suggesting NO could stimulate renin secretion through the macula densa pathway. To test whether neuronal NOS mediates renin secretion, renin was stimulated by either the renal baroreceptor or the diuretic furosemide (acting through the macula densa pathway). Renin secretion rate (RSR) was measured in 12 Inactin-anesthetized rats at normal (104 +/- 3 mmHg) and reduced renal perfusion pressure (65 +/- 1 mmHg), before and after selective blockade of the neuronal NOS with 7-nitroindazole (7-NI, 50 mg/kg ip). 7-NI had no effect on basal blood pressure (102 +/- 2 mmHg) or renal blood flow (RBF). Decreasing renal perfusion pressure doubled RSR from 11.8 +/- 3.3 to 22.9 +/- 5.7 ng ANG I.h-1.min-1 (P < 0.01) (ANG I is angiotensin I). Similarly, in 7-NI-treated rats, reduced perfusion doubled RSR from 8.5 +/- 1.8 to 20.5 +/- 6.2 ng ANG I.h-1.min-1 (P < 0.01). Renal hemodynamics and RSR were measured in response to 5 mg/kg iv furosemide in 12 control rats and 11 rats treated with 7-NI. Blocking neuronal NOS did not alter blood pressure (102 +/- 2 mmHg), RBF (5.8 +/- 0.4 ml.min-1.g kidney wt-1), or renal vascular resistance (18.7 +/- 1.4 mmHg.ml-1.min.g kidney wt).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Splice variants of neuronal nitric oxide synthase are present in the rat kidney

2008 ◽  
Vol 24 (5) ◽  
pp. 1422-1428 ◽  
Author(s):  
C. Smith ◽  
M. Merchant ◽  
A. Fekete ◽  
H.-L. Nyugen ◽  
P. Oh ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Splice Variants ◽  
Rat Kidney ◽  
Neuronal Nitric Oxide Synthase ◽  
Oxide Synthase

Regulation of renal CYP4A expression and 20-HETE synthesis by nitric oxide in pregnant rats

2003 ◽  
Vol 285 (2) ◽  
pp. F295-F302 ◽  
Author(s):  
Mong-Heng Wang ◽  
Jishi Wang ◽  
Hsin-Hsin Chang ◽  
Barbara A. Zand ◽  
Miao Jiang ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Rat Kidney ◽  
Late Pregnancy ◽  
Inhibitory Effect ◽  
Female Rats ◽  
Male Rats ◽  
Pregnant Rats ◽  
Renal Vasoconstriction ◽  
Dependent Inhibition

20-Hydroxyeicosatetraenoic acid (20-HETE), which promotes renal vasoconstriction, is formed in the rat kidney primarily by cytochrome P-450 (CYP) 4A isoforms (4A1, 4A2, 4A3, 4A8). Nitric oxide (NO) has been shown to bind to the heme moiety of the CYP4A2 protein and to inhibit 20-HETE synthesis in renal arterioles of male rats. However, it is not known whether NO interacts with and affects the activity of CYP4A1 and CYP4A3, the major renal CYP4A isoforms in female rats. Incubation of recombinant CYP4A1 and 4A3 proteins with sodium nitroprusside (SNP) shifted the absorbance at 440 nm, indicating the formation of a ferric-nitrosyl-CYP4A complex. The absorbance for CYP4A3 was about twofold higher than that of CYP4A1. Incubation of SNP or peroxynitrite (PN; 0.01–1 mM) with CYP4A recombinant membranes caused a concentration-dependent inhibition of 20-HETE synthesis, with both chemicals having a greater inhibitory effect on CYP4A3-catalyzed activity. Moreover, incubation of CYP4A1 and 4A3 proteins with PN (1 mM) resulted in nitration of tyrosine residues in both proteins. In addition, PN and SNP inhibited 20-HETE synthesis in renal microvessels from female rats by 65 and 59%, respectively. We previously showed that microvessel CYP4A1/CYP4A3 expression and 20-HETE synthesis are decreased in late pregnancy. Therefore, we investigated whether such a decrease is dependent on NO, the synthesis of which has been shown to increase in late pregnancy. Administration of NG-nitro-l-arginine methyl ester (l-NAME) to pregnant rats for 6 days ( days 15- 20 of pregnancy) caused a significant increase in systolic blood pressure, which was prevented by concurrent treatment with the CYP4A inhibitor 1-aminobenzotriazole (ABT). Urinary NO2/NO3 excretion decreased by 40 and 52% in l-NAME- and l-NAME + ABT-treated groups, respectively. Interestingly, renal microvessel 20-HETE synthesis showed a marked increase following l-NAME treatment, and this increase was diminished with coadministration of ABT. These results demonstrate that NO interacts with CYP4A proteins in a distinct manner and it interferes with renal microvessel 20-HETE synthesis, which may play an important role in the regulation of blood pressure and renal function during pregnancy.

Depolarization of the macula densa induces superoxide production via NAD(P)H oxidase

2007 ◽  
Vol 292 (6) ◽  
pp. F1867-F1872 ◽  
Author(s):  
Ruisheng Liu ◽  
Jeffrey L. Garvin ◽  
YiLin Ren ◽  
Patrick J. Pagano ◽  
Oscar A. Carretero
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Oxidase Inhibitor ◽  
Fluorescent Dye ◽  
Macula Densa ◽  
Superoxide Production ◽  
Tubuloglomerular Feedback ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Nacl Concentration

Superoxide (O2−) enhances tubuloglomerular feedback by scavenging nitric oxide at the macula densa. However, the singling pathway of O2− production in the macula densa is not known. We hypothesized that the increase in tubular NaCl concentration that initiates tubuloglomerular feedback induces O2− production by the macula densa via NAD(P)H oxidase, which is activated by macula densa depolarization. We isolated and microperfused the thick ascending limb of the loop of Henle and attached macula densa in rabbits. A fluorescent dye, dihydroethidium, was used to detect O2− production at the macula densa. When luminal NaCl was switched from 10 to 80 mM, a situation of initiating maximum tubuloglomerular feedback response, O2− production significantly increased. To make sure that the shifts in the oxyethidium/dihydroethidium ratio were due to changes in O2−, we used tempol (10−4 M), a stable membrane-permeant superoxide dismutase mimetic. With tempol present, when we switched from 10 to 80 mM NaCl, the increase in oxyethidium/dihydroethidium ratio was blocked. To determine the source of O2−, we used the NAD(P)H oxidase inhibitor apocynin. When luminal NaCl was switched from 10 to 80 mM in the presence of apocynin, O2− production was inhibited by 80%. To see whether the effect of increasing luminal NaCl involves Na-K-2Cl cotransporters, we inhibited them with furosemide. When luminal NaCl was switched from 10 to 80 mM in the presence of furosemide, O2− production was blocked. To test whether depolarization of the macula densa induces O2− production, we artificially induced depolarization by adding valinomycin (10−6 M) and 25 mM KCl to the luminal perfusate. Depolarization alone significantly increases O2− production. We conclude that increasing luminal NaCl induces O2− production during tubuloglomerular feedback. O2− generated by the macula densa is primarily derived from NAD(P)H oxidase and is induced by depolarization.

scholarly journals Evaluation of hemodynamic renal in the isolated perfused rat kidney after nitric oxide blockade

2008 ◽  
Vol 22 (S1) ◽  
Author(s):  
Patricia Fiorino ◽  
Vera Azevedo Farah ◽  
Kalebe G Darini ◽  
Iara Cristina Araujo ◽  
Ana Paula Oliveira Leite ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Rat Kidney ◽  
Isolated Perfused Rat Kidney ◽  
Perfused Rat Kidney

scholarly journals Expression of Immunoreactive Nitric Oxide Synthase Isoforms in Rat Kidney. Effects of Dietary Salt and Losartan.

1995 ◽  
Vol 36 (3) ◽  
pp. 389-398 ◽  
Author(s):  
Akihiro TOJO ◽  
Kirsten M. MADSEN ◽  
Christopher S. WILCOX
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Rat Kidney ◽  
Dietary Salt ◽  
Oxide Synthase

Expression of endothelial nitric oxide synthase in developing rat kidney

2005 ◽  
Vol 288 (4) ◽  
pp. F694-F702 ◽  
Author(s):  
Ki-Hwan Han ◽  
Jung-Mi Lim ◽  
Wan-Young Kim ◽  
Hyang Kim ◽  
Kirsten M. Madsen ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Cells ◽  
Kidney Development ◽  
Early Stage ◽  
Rat Kidney ◽  
Immunoblot Analysis ◽  
Renal Hemodynamics ◽  
Vascular Bundles ◽  
Peritubular Capillaries ◽  
Endothelial Nitric Oxide

Endothelium-derived nitric oxide (NO) is synthesized within the developing kidney and may play a crucial role in the regulation of renal hemodynamics. The purpose of this study was to establish the expression and intrarenal localization of the NO-synthesizing enzyme endothelial NO synthase (eNOS) during kidney development. Rat kidneys from 14 ( E14)-, 16 ( E16)-, 18 ( E18)-, and 20-day-old ( E20) fetuses and 1 ( P1)-, 3 ( P3)-, 7 ( P7)-, 14 ( P14)-, and 21-day-old ( P21) pups were processed for immunocytochemical and immunoblot analysis. In fetal kidneys, expression of eNOS was first observed in the endothelial cells of the undifferentiated intrarenal capillary network at E14. At E16, strong eNOS immunoreactivity was observed in the endothelial cells of renal vesicles, S-shaped bodies (stage II glomeruli), and stage III glomeruli at the corticomedullary junction. At E18- 20, early-stage developing glomeruli located in the subcapsular region showed less strong eNOS immunoreactivity than those of E16. The eNOS-positive immature glomeruli were observed in the nephrogenic zone until 7 days after birth. In fetal kidneys, eNOS was also expressed in the medulla in the endothelial cells of the capillaries surrounding medullary collecting ducts. After birth, eNOS immunostaining gradually increased in the developing vascular bundles and peritubular capillaries in the medulla and was highest at P21. Surprisingly, eNOS was also expressed in proximal tubules, in the endocytic vacuolar apparatus, only at P1. The strong expression of eNOS in the early stages of developing glomeruli and vasculature suggests that eNOS may play a role in regulating renal hemodynamics of the immature kidney.

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