[Effects of nitric oxide synthase inhibitors on cerebral mitochondrial structure and function in fetal rats with intrauterine distress].
OBJECTIVE
To evaluate the effects of different types of nitric oxide synthase (NOS) inhibitors on cerebral mitochondrial structure and function in fetal rats with intrauterine distress.


METHODS
Rats were divided into control group, acute ischemia group, treatment group 1 injection of [N omega-nitro-L-arginine (L-NNA) 4 mg/kg into pregnant rats' abdomen before ischemia], reperfusion group, treatment group 2 [injection of L-NNA 4 mg/kg into pregnant rats' abdomen before ischemia followed by injection of aminoguanidine (AG) 500 mg/kg before operation]. Changes of mitochondrial structure were observed by transmission electron microscopy and expression of neuronal nitric oxide synthase (nNOS) mRNA(A) through RT-PCR. Inducible nitric oxide synthase (iNOS) activity and mitochondrial Na(+)K(+)-ATPase and cytochrome oxidase activity were measured.


RESULTS
(1) The A of NOS (5 min, 15 min) in acute ischemia group was higher than that of treatment group 1 (P < 0.05). There was no difference between the A of nNOS (30 min) in two groups (P > 0.05). But the A of nNOS in two groups was higher than that in control group (P < 0.05). (2) iNOS activities in reperfusion group were all higher than those in treatment group 2. Both of those in two groups were higher than that in control group (P < 0.05). (3) Mitochondrial Rsv (5 min, 15 min) in acute ischemia group was smaller than those of treatment group 1 (P < 0.05). There was no difference between mitochondrial Rsv (30 min) in two groups (P > 0.05). Mitochondrial Rsv in reperfusion group was all smaller than those in treatment group 2. And mitochondrial Rsv in all the groups was smaller than that in control group (P < 0.05). (4) Na(+)K(+)-ATPase activity in treatment group 2 was higher than those in reperfusion group (P < 0.05). Na(+)K(+)-ATPase activity in two groups was lower than that in control group (P < 0.05).


CONCLUSIONS
nNOS and iNOS play a role in cerebral mitochondrial structure and function damage in fetal rats with intrauterine distress. L-NNA has some limited treatment effect on mitochondrial damage when intrauterine distress induces acute fetal hypoxic-ischemic brain damage. AG plays an obvious treatment role in mitochondrial damage during reperfusion following ischemia.
Zhang
Hua
H
Department of Obstetrics and Gynecology, First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
Yao
Zhen-wei
ZW
Wu
Wei-xin
WX
D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000648:ultrastructure; D005260:Female; D005316:Fetal Distress / Q000201:enzymology / Q000473:pathology*; D006146:Guanidines / Q000494:pharmacology*; D008928:Mitochondria / Q000201:enzymology* / Q000648:ultrastructure; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D011247:Pregnancy; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism
D006146:Guanidines; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat; D000254:Sodium-Potassium-Exchanging ATPase; C004479:pimagedine