Antithrombin III (AT III) prevents experimentally induced hypertension and proteinuria in pregnant stroke-prone spontaneously hypertensive rats (SHRSP)

• Published in: Japanese Journal of Pharmacology 1995, Vol.67 (suppl.2), p.278-278
• Main Authors: Shinyama, Hiroshi, Marita, Yuji, Akira, Toshiaki, Uchida, Takeshi, Hirahara, Keizo
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)47076-5

Preeclampsia, a syndrome characterized by gestational hypertension, excessive proteinuria and generalized edema, is a major cause of both fetal and maternal morbidity and mortality of pregnancy. A current concept of the pathogeneses of preeclampsia is based on a coagulatory disorder. To give an evidence for preventive effects of AT III, a serine protease inhibitor with anti-thrombin activity, on preeclampsia, we examined the effect of consecutive treatment with AT III on the progressive increase in blood pressure and proteinuria with gestational day, typically in pregnant SHRSP fed a high-salt diet. AT III, administered i.v. at doses of 30-300 U/kg/day, from the next day of mating to the day before delivery (term 20-22 days), suppressed both the progress of the hypertension and the proteinuria, in a dose-dependent manner, whereas it did not affect the urine volume, electrolyte excretion and off-springs weight. There was an obyious correlation of the degree of prevention between hypertension and proteinuria. Histological determination of the kidney also suggested the effectiveness of AT III in preventing the analogous structural abnormalities such as glomerulosclerosis, generally seen in human preeclampsia. These results may manifest that salt-loading elicits exaggerated hypertension and proteinuria in pregnant SHRSP similar to human preeclampsia, and that AT III ameliorates these alterations. Similarly, this may account for the rationale of the treatment of human preeclampsia with this anticoagulant.