Comparison of the effects of vasopressin and norepinephrine on organ perfusion during septic shock in streptozotocin-induced diabetic rats.
OBJECTIVE
The purpose of this study was to compare the effects of norepinephrine (NE) and vasopressin on systemic hemodynamics, renal and mesenteric artery blood flow, inflammatory response and inducible nitric oxide synthase (iNOS) activity during endotoxin shock in streptozotocin-induced diabetic rats.


METHODS
The study was designed to include three sets of experiments: (1) measurement of changes in systemic hemodynamics and mesenteric and renal artery blood flow; (2) measurement of biochemical variables; and (3) measurement of iNOS activity in the mesenteric artery. Systemic hemodynamics, regional artery blood flow changes and biochemical variables were assessed before treatment and 1, 2 and 3 h after treatment.


RESULTS
Vasopressin, but not NE, prevented the decreases in aortic blood flow, but did not restore mesenteric artery blood flow. In addition, vasopressin partially restored renal artery blood flow in diabetic rats. Plasma nitrite levels and iNOS activity in the mesenteric artery were elevated after intravenous LPS in diabetic rats. Endotoxin-induced decreases in mesenteric arterial blood flow were partially restored by vasopressin with nonselective NOS inhibitor, N G-nitro-l-arginine methyl ester (l-NAME), in diabetic rats. Moreover, l-NAME prevented increases in plasma nitrite levels and iNOS activity in the mesenteric artery. In contrast, endotoxin-induced decreases in renal arterial blood flow were partially restored by vasopressin with l-NAME, but not by NE in diabetic rats.


CONCLUSIONS
Nitric oxide may be one possible contributor to reduced sensitivity of the mesenteric and renal arteries to vasopressin during septic shock in streptozotocin-induced diabetic rats.
Hinohara
Hiroshi
H
Department of Anesthesiology, Graduate School of Medicine, Gunma University, 3-39-22 Showa-Machi, Maebashi, Gunma 371-8511, Japan.
Kadoi
Yuji
Y
Tokue
Aya
A
Saito
Shigeru
S
Kawauchi
Chikara
C
Mizutani
Akio
A
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000187:drug effects; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology; D013152:Splanchnic Circulation / Q000187:drug effects; D013311:Streptozocin; D014667:Vasopressins / Q000494:pharmacology*
D014667:Vasopressins; D009569:Nitric Oxide; D013311:Streptozocin; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine
J Infect Dis. 1998 Jan;177(1):127-32
9419179
Br J Pharmacol. 1973 Jan;47(1):12-25
4123817
J Mol Cell Cardiol. 1997 Sep;29(9):2393-402
9299363
J Biol Chem. 2005 Mar 18;280(11):10040-6
15647265
Crit Care Med. 1996 Jun;24(6):1083-6
8681578
Crit Care Med. 2003 Jun;31(6):1659-67
12794401
Shock. 1996 Feb;5(2):116-21
8705388
J Surg Res. 2002 Nov;108(1):69-76
12443717
J Chem Neuroanat. 2000 Jan;17(4):199-206
10697246
Crit Care Med. 1999 Mar;27(3):639-60
10199548
J Nephrol. 2001 Mar-Apr;14(2):110-4
11411011
Crit Care Med. 2004 Jun;32(6):1327-31
15187515
Crit Care Med. 2002 Jun;30(6):1334-9
12072691
Cardiovasc Res. 2004 Nov 1;64(2):298-307
15485689
Crit Care Med. 1993 Feb;21(2 Suppl):S19-24
8428492
Br J Pharmacol. 1996 Aug;118(7):1848-54
8842453
Circulation. 2002 Oct 15;106(16):2067-72
12379575
Acta Anaesthesiol Scand. 2008 May;52(5):664-72
18261198
J Hypertens. 1999 May;17(5):673-8
10403611
Shock. 2007 Nov;28(5):602-9
17607161
Ann Surg. 1998 Aug;228(2):239-48
9712570
Crit Care Med. 2000 Jul;28(7):2500-6
10921585
Acta Anaesthesiol Scand Suppl. 1995;107:239-48
8599285
Crit Care Med. 2001 Mar;29(3):487-93
11373409
Circ Res. 2007 Jan 5;100(1):130-9
17138944
Br J Anaesth. 2005 May;94(5):563-8
15734782
J Appl Physiol (1985). 2003 Aug;95(2):803-9
12851422
J Pharmacol Exp Ther. 2001 Feb;296(2):252-9
11160605
J Biol Chem. 2002 Sep 13;277(37):33776-82
12097323
Crit Care Med. 2003 Nov;31(11):2646-50
14605537
Acta Anaesthesiol Scand. 1999 Mar;43(3):275-88
10081533
Anesth Analg. 2003 Dec;97(6):1756-1763
14633555
Intensive Care Med. 1996 Dec;22(12):1354-9
8986486
J Pharmacol Exp Ther. 1997 Jul;282(1):475-84
9223590
Crit Care Med. 1996 Feb;24(2):298-305
8605805
Anesth Analg. 2004 Jul;99(1):212-220
15281532
J Surg Res. 1996 Mar;61(2):496-502
8656632
Intensive Care Med. 2003 Oct;29(10):1774-81
12698246