[Effects of aminoguanidine in different dosages on renal function in endotoxin induced rabbits shock model].
OBJECTIVE
To explore the effects of aminoguanidine (AG) in different dosages on renal function in endotoxin induced rabbits shock model in the early stage and to approve the effects of dose-depended and time-depended of AG.


METHODS
Fourty New Zealand rabbits under anaesthesia were randomly divided into 5 groups: sham group, LPS group, the first group of AG, the second group of AG, the third group of AG. Each rabbits from the four groups received Escherichia Coli O55B5 LPS 400 micro g/kg to induce endotoxic shock except sham group. Edotoxic shock was diagnosed when the mean arterial pressure (MAP) decreased to 30%. Each rabbits in sham group and LPS group received 5ml NS, in the other three groups were infused with AG 30 mg/kg (the first group of AG), 50 mg/kg (the second group of AG), 100 mg/kg (the third group of AG) in 5ml NS, respectively. Urine output was recorded at the following time points, before injecting IPS (T(0)), shock (T), 1 h (T(1)), 2 h (T(2)), 3 h (T(3)), 4 h (T(4)), 5 h (T(5)) and 6 h (T(6)) after shock. Plasma nitrate and nitrite (NO(3)(-)/NO(2)(-), stable products of NO), BUN, Scr, RBP were determined at the time points of T, T(2), T(4) and T(6).


RESULTS
LPS increased NO(3)(-)/NO(2)(-), BUN, Scr, RBP [from (47 +/- 5) micro mol/L, (5.8 +/- 1.5) mmol/L, (41 +/- 10) micro mol/L, (240 +/- 61) ng/L (T(0)) to (160 +/- 18) micro mol/L, (15.5 +/- 1.8) mmol/L, (166 +/- 23) micro mol/L, (1580 +/- 180) ng/L (T(6)), respectively, P < 0.01]; Urine output decreased significantly [from (17.6 +/- 2.8) ml (T(0)) to (1.3 +/- 0.6) ml (T(6)), P < 0.01]. AG attenuates the increasing of NO(3)(-)/NO(2)(-), BUN, Scr and RBP, and decreasing of urine output. NO(3)(-)/NO(2)(-) of the first, second and third group of AG at T(6) were (58 +/- 8), (50 +/- 14) and (46 +/- 9) micro mol/L, respectively. Compared to LPS group, there was a significant difference (P < 0.01). BUN was (8.2 +/- 2.9), (7.5 +/- 1.9) and (5.5 +/- 1.8) mmol/L, respectively at T(6). Compared to LPS group, there was a significant deference (P < 0.01). RBP was (350 +/- 60), (272 +/- 72) and (248 +/- 103) ng/L, respectively at T(6) (compared to LPS group, there was a significant deference. P < 0.05, < 0.05, < 0.01). Urine output was (11. 1 +/- 2.4), (12. 1 +/- 1. 3) and (17.1 +/- 2. 4) ml, respectively on T(6) (compared to LPS group, there was a significant deference, P < 0.01). AG of 100 mg/kg showed the best effect among three AG groups.


CONCLUSIONS
AG inhibited NO formation in dose-depended and time depended way. AG attenuated the changes of renal function induced by NO.
Wang
Lei
L
ICU, Beijing Children's Hospital, Capital University of Medical Sciences, Beijing 100045, China.
Fan
Xun-mei
XM
Tang
Hao-xun
HX
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use; D005260:Female; D006146:Guanidines / Q000008:administration & dosage / Q000627:therapeutic use*; D007677:Kidney Function Tests; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D011817:Rabbits; D011897:Random Allocation; D012772:Shock, Septic / Q000188:drug therapy*; D016896:Treatment Outcome
D004791:Enzyme Inhibitors; D006146:Guanidines; D019001:Nitric Oxide Synthase; C004479:pimagedine