Nitric oxide synthase inhibition aggravates the adverse renal effects of high but not low intraabdominal pressure.
BACKGROUND
Previously, the authors demonstrated that an intraabdominal pressure (IAP) of 14 mmHg in normal rats reduced kidney function/hemodynamics. These adverse effects are related to interference with the nitric oxide (NO) system. This study was designed to compare the effects of NO synthase (NOS) inhibition on kidney function/hemodynamics during increases in IAP from 0 mmHg to 7, 10, and 14 mmHg.


METHODS
The rats were divided into six groups. After an IAP of 0 (baseline), the first three groups were subjected to increasing IAPs as follows: 7 mmHg (group 1), 10 mmHg (group 2), and 14 mmHg (group 3). Each pressure was applied for 1 h, followed by a deflation period of 60 min (recovery). An additional three groups were pretreated with nitro-L: -arginine methyl ester (L: -NAME), an NOS inhibitor, before pressures of 7 mmHg (group 4), 10 mmHg (group 5) and 14 mmHg (group 6) were applied for 1 h. Urine flow rate (V), Na(+) excretion (U(Na)V), glomerular filtration rate (GFR), and renal plasma flow (RPF), were determined throughout the experiments.


RESULTS
There were no significant changes in V, U(Na)V, GFR, or RPF during 7-mmHg insufflation. However, significant reductions in these parameters were observed during 10 and 14 mmHg, with V decreasing from 9.95 + or - 1.34 microl/min to 6.8 + or - 1.1 and 6.1 + or - 0.5 microl/min (p < 0.05) and U(Na)V decreasing from 1.29 + or - 0.28 to 0.43 + or - 0.32 muEq/min (p < 0.05), and 0.39 + or - 0.09 muEq/min (p < 0.05). These alterations in excretory functions were associated with considerable declines in GFR, from 1.98 + or - 0.2 to 1.05 + or - 0.18 ml/min (p < 0.05) and 0.95 + or - 0.06 ml/min (p < 0.05) and RPF from 8.66 + or - 0.62 to 3.94 + or - 0.88 ml/min (p < 0.05) and 3.08 + or - 0.71 ml/min (p < 0.05), respectively. When the animals were pretreated with L: -NAME, the adverse renal effects of an IAP of 14 mmHg, but not 10 mmHg, were substantially aggravated.


CONCLUSIONS
Decreased renal function/perfusion is induced by IAP pressures of 10 and 14 mmHg but not 7 mmHg. Inhibition of NOS aggravates the adverse renal effects of high (14 mmHg) but not low (7 or 10 mmHg) IAP, indicating that NO deficiency may contribute to the renal dysfunction during high IAP.
Bishara
Bishara
B
Department of General Surgery "A", Rambam-Human Health Care Campus and Faculty of Medicine, Technion-Israel Institute of Technology, P.O. Box 9649, Haifa 31096, Israel.
Ramadan
Rawi
R
Karram
Tony
T
Awad
Hoda
H
Abu-Saleh
Niroz
N
Winaver
Joseph
J
Assadi
Akram
A
Abassi
Zaid
Z
D000704:Analysis of Variance; D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology*; D007677:Kidney Function Tests; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D011028:Pneumoperitoneum, Artificial / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester
Ann Surg. 2000 Feb;231(2):195-201
10674610
Am J Physiol. 1991 Dec;261(6 Pt 2):F1033-7
1750517
Surg Endosc. 2007 Feb;21(2):152-60
17160650
Surg Endosc. 2003 May;17(5):819-24
12584602
Surg Endosc. 2009 Mar;23(3):568-76
18363060
J Biol Chem. 1992 Jun 15;267(17):12336-40
1318315
J Endourol. 1998 Apr;12(2):95-100
9607433
Transplant Proc. 1997 Dec;29(8):3402-3
9414765
Surg Endosc. 2004 Jun;18(6):919-23
15108115
Nephrol Dial Transplant. 2003 Nov;18(11):2269-77
14551353
Hypertension. 1992 Jun;19(6 Pt 2):766-9
1592478
Am J Physiol Regul Integr Comp Physiol. 2008 Mar;294(3):R842-50
18160528
Antioxid Redox Signal. 2003 Apr;5(2):181-94
12716478
J Urol. 2008 Oct;180(4):1554-8
18710725
J Endourol. 1998 Apr;12(2):193-7
9607449
Surg Endosc. 2009 Apr;23(4):776-82
18629585
J Am Coll Surg. 1996 Apr;182(4):317-28
8605555
Nat Clin Pract Endocrinol Metab. 2007 Jan;3(1):46-56
17179929
BJU Int. 1999 Jun;83(9):944-7
10368233
Ann Surg. 1983 Feb;197(2):183-7
6600601
J Surg Res. 1996 Jan;60(1):61-8
8592433
Ann Surg. 1982 Nov;196(5):594-7
7125746
J Clin Invest. 1945 May;24(3):388-404
16695228
Surg Endosc. 2001 Feb;15(2):183-8
11285964
Urology. 1994 Apr;43(4):453-9
8154067
J Am Coll Cardiol. 1998 Nov;32(5):1389-96
9809953
J Endourol. 1994 Apr;8(2):99-103
8061681
Surg Endosc. 2003 Jul;17(7):1092-7
12632126
Surg Endosc. 2003 Aug;17(8):1231-6
12799887
Semin Nephrol. 2004 Jul;24(4):299-315
15252770
Am Surg. 2003 Apr;69(4):300-3; discussion 303
12716087
J Endourol. 2005 Oct;19(8):1026-31
16253075
J Am Coll Surg. 2002 Oct;195(4):476-83
12375752
Ann Surg. 2003 Mar;237(3):351-7
12616118
Pharmacol Ther. 2008 Dec;120(3):333-9
18930078
J Endourol. 1994 Oct;8(5):349-52
7858621
Eur J Pharmacol. 1989 Jan 24;160(1):193-4
2540991
Hypertension. 1998 Oct;32(4):746-52
9774374
Surgery. 1997 Feb;121(2):206-11
9037233
Surg Endosc. 2003 Mar;17(3):480-4
12415336
Nature. 1990 Dec 20-27;348(6303):730-2
2175396
Pharmacol Rev. 1991 Jun;43(2):109-42
1852778
J Surg Res. 1995 Oct;59(4):497-503
7564324
Transplantation. 1999 Mar 15;67(5):722-8
10096529