Increased Glomerular Nitric Oxide Synthesis in ...

Renal Failure

ISSN: 0886-022X (Print) 1525-6049 (Online) Journal homepage: http://www.tandfonline.com/loi/irnf20

Increased Glomerular Nitric Oxide Synthesis in Ischemic Acute Renal Failure in the Rat Lina Rivas-Cabañero, José M. Valdivielso & José M. López-Novoa To cite this article: Lina Rivas-Cabañero, José M. Valdivielso & José M. López-Novoa (1995) Increased Glomerular Nitric Oxide Synthesis in Ischemic Acute Renal Failure in the Rat, Renal Failure, 17:4, 479-481, DOI: 10.3109/08860229509037612 To link to this article: https://doi.org/10.3109/08860229509037612

Published online: 07 Jul 2009.

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Date: 04 January 2018, At: 02:20

Renal Failure, 17(4), 479-481 (1995)

LETTER T O THE EDITOR

Downloaded by [179.61.164.44] at 02:20 04 January 2018

Increased Glomerular Nitric Oxide Synthesis in Ischemic Acute Renal Failure in the Rat

Acute renal failure (ARF) following renal ischemia is characterized by changes in renal hemodynamics, tubular obstruction, backleak of filtrate, and changes in vascular reactivity. Renal vascular resistance is increased in the first few hours following ischemic injury (1). In rats with ischemic ARF, inhibition of nitric oxide (NO) synthesis by L-NAME aggravates the renal injury. This effect is abolished by pretreatment with L-arginine, thus suggesting a protective role of NO in ischemic-induced ARE Thus, the present study was designed to determine the nitric oxide production by isolated glomeruli after renal ischemia and reperfusion. Ischemia was induced in female Wistar rats (250 g) by clamping both renal arteries. After 1 h of ischemia rats were divided in two groups. Blood reperfusion was allowed for 2 h in one group (n= 13) and for 24 h in the other (n = 12). Two groups of sham-operated rats were used as control ( n = 10 and n = 13, respectively). A blood sample was obtained and plasma creatinine was measured by a modification of Jaff6 reaction. Glomeruli were obtained as previously described (2). The final preparation consisted of glomeruli without Bowman's capsule and without afferent or efferent arterioles. Tubular contamination was less than 5%, and glomerular cell viability was higher than 95%. Glomeruli were plated out in 4 x 6 well plates (7000 glomeruli per well) and incubated for 24 h at 37OC in sterile conditions, in RPMI 1640, endotoxin-free, with Phenol red culture medium (Gibco) supplemented with 10% fetal calf serum, penicillin (10.66 pg/mL), and polymyxin (2.5 pg/mL). Nitrite production was determined in the supernatant by a colorimetric quantitative method based on Griess reaction (3). Data on plasma creatinine and glomerular nitrite production are shown in Fig. 1. Rats with 24 h of reperfusion after 1 h of ischemia showed significantly higher levels of plasma creatinine with respect to all the other groups. Glomerular nitric oxide synthesis, tested as nitrite production, was significantly higher in rats with ischemia and 24 h of reperfusion than in all the others groups. Nitrite production was similar in rats with ischemia and 2-h reperfusion than in sham-operated rats. This increased glomerular NO synthesis after renal ischemia could suggest a protective role of NO in ischemic ARE Increased glomeruli NO synthesis has been also described in rats with gentamicin-induced renal failure (4). The mechanism responsible for increased glomerular NO synthesis in renal failure could be related to the increased renal release of endothelin after renal ischemia (5). Endothelin has 419


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Letter to the Editor

SHAY2H

tSCH2H SHAM24H lSCH24H

GROUPS Figure 1. Plasma creatinine (lower panel) and glomerular nitrite production (upper panel) in shamoperated rats and rats with ischemic acute renal failure. Abbreviations: S H A M 2H: sham operated with 2-h recirculation; SHAM 24 H: sham-operated rats with 24-h recirculation; ISCH 2 H: 1-h ischemia and 2-h recirculation; ISCH 24 H: 1-h ischeFa and 24-h recirculation. Statistical significance: p < 0.01: *versus SHAM 2 H; #versus ISCH 2H; tversus SHAM 24 H.

been reported to increase glomerular NO synthesis through the activation of ET, receptors (6). This effect seems to need some time to occur, since rats with ischemia and only 2 h of reperfusion did not show any increase in glomerular nitrite production. Another possibility is that some substance present in uremic plasma could be responsible for activating NO synthesis. Increased glomerular NO production in ischemic ARF could play a role counteracting the vboconstrictor effects of substances such as endothelin, released by the kidney after renal ischemia.

ACKN0WLEDGME;NTS This work has been supported by a grant from DGICYT (SAF 93/92). L. RivasCabaiiero is supported by a research fellowship of the University of Salamanca.

REFERENCES 1,

Conger JD, Robinette JB, Hammond WS: Dinerences in vascular reactivity in models of ischemia acute renal failure. Kidney Inr 39:1087-1097, 1991.

Letter to the Editor

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2. Olivera A, Mpez-Novoa JM: Effects of adenosine and adenosine analogues on CAMP accumulation in cultured rat mesangial cells and isolated glomeruli. Br J Phannacol 107:341-346, 1992. 3. Cattell V,Largen P,de Heer E, Cook T Glomeruli synthesize nitrite in active Heymann nephritis: the source is infiltrating macrophages. Kidney In? 40347-851, 1991. 4. Rivas-Cabaiiero L, Montero A, Mpez-Novoa JM: Increased glomerular nitric oxide synthesis in gentamicininduced renal failure. Eur J Phmmacol270:119-121, 1994. 5. M p e z - F a d A, G6mez-Garre D, Bemabeu F, L6pez-Novoa JM: A role for endothelin in the maintenance of post-ischaemic renal failure in the rat. J Physiol 444:513-522, 1991. 6. Edwars RM, Pullen M, Nambi P: Activation of endothelin ET, receptors increases glomerular cGMP via an L-arginine dependent pathway. Am I Physiol 263:F1020-F1025, 1992.


Lina Rivas-Cabafiero, JosC M. Valdivielso, and JosC M. L6pez-Novoa Instituto Reina Sofia de Investigaciones NefroMgicas, Departamento de Fisiologia y Farmacologia, Universidad de Salamanca, Salamanca, Spain

Address correspondence to: Prof. Jost M. L6pez-Novoa, Departamento de Fisiologia y Farmacologia, Edificio

Departamental, Campus Miguel de Unamuno, Universidad de Salamanca, Avenida Campo Charro sln. 37007 Salamanca, Spain. Fax: 34-23-294669.