Experimental animal model for preeclampsia by the infusion of nitric oxide synthase inhibitor and reverse of preeclampsia by high dose L-arginine infusion / 대한산부인과학회잡지

ABSTRACT

OBJECTIVES: To learn which inhibition of nitric oxide synthase with L-nitro arginine methylester(L-NAME) induces a preeclampsia-like syndrome in pregnant rabbits and high dose of L-arginine reverse the adverse changes induced by nitric oxide synthesis inhibition in pregnant rabbits. MTERIAL AND METHOD: Twenty Newzealand rabbits with 22-days of gestation were injected subcutaneously with 400mg of L-NAME for 7days and 100mg/kg L-arginine was also given intravenously 10 of 20 L-NAME injected pregnant rabbits. They are compared with the control group in which same volume of saline was subcutaneously injected to 5 rabbits with same condition. They were anesthesized by ketamine 50 mg/kg and roupum 2 mg/kg intramuscularly. Cutdown of femoral artery was performed and 22 gauge angioneedle was inserted. On manometer,three way catheter was connected, zeroed with saline, and blood pressure was read. Blood samples were taken from the vein of ear and checked for count of blood cells and bood chemistry (BUN/Cr, GOT/GPT, LDH, Uric acid). Urine protein was measured with nelaton catheterized urine. We injected drugs for 7 days begining on 22 days after mating and performed cesarian section to deliver fetus. To observe their effects on organs, lung, liver, placenta and kidney were taken and fixed with formalin. The sliced kidney tissue in thickness of 1 mm, was fixed with glutaraldehyde for electron microscopy and stored at 4degree C. Special staining was done for closed observation of pattern changes. For statistical analysis, mean+/-SEM was used. The control and experimental groups were compared by unpaired t-test and the differences were significant if probability level is less than 0.05(<0.05). RESULT: Mean blood pressure(MAP) in the experimental group I was significantly high compared to the control group(P<0.05). There was no significant differences in MAP between experimental group II and control group. Urine Protein, BUN, Cr, GOT/GPT, LDH, platelet count in the experimental group I was significantly high(p<0.05) compared to the control group. There was no significant difference between experimental group II and control group. In light microscopic examination, lung, liver, kidney, placenta showed specific finding in experimental group I. Misconstructive of glomerulus in the experimental kidney was well preserved under EM examination. Interstitium of kidney was widened by increase of mesangial matrix. Mild effacement of foot process and cytoplasm of proximal tubule containing electron dense myelin figure like structure were observed. CONCLUSION: Long term injection of L-arginine analogue produced preeclampsia like syndrome and pathologic changes of organ system in pregnant rabbits. Concurrent high dose of L-arginine reversed such chages.