ANTITHROMBIN-III PREVENTS BLOOD-PRESSURE ELEVATION AND PROTEINURIA INDUCED BY HIGH-SALT INTAKE IN PREGNANT STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

In pregnant stroke-prone spontaneously hypertensive rats, salt-loading causes symptoms similar to those of human preeclampsia, such as hyper tension and proteinuria. To seek evidence of the therapeutic potential in preeclampsia of antithrombin III (AT III), which is a serine prote ase inhibitor active on various enzymes of the coagulation cascade, we examined the effect of consecutive treatment with AT III on hypertens ion and proteinuria in this animal model. Salt-loading (2% NaCl diet) caused a significant elevation of systolic blood pressure on day 15-17 and of urinary protein excretion on day 17-19 of gestation, as compar ed with animals fed a normal diet. AT III, administered i.v. at a dose of 60 or 300 U/kg/d for 10 d from day 9-11 to 18-20, attenuated these pathological changes in a dose-dependent manner. Histological examina tion of the kidney revealed that AT III prevented the occurrence of ar teriosclerosis and thickening of the capillary basement membrane. Howe ver, the pathological changes induced by salt-loading were not attribu table to activation of the blood coagulation. system. These results de monstrate that AT III has preventive action against salt-induced hyper tension and proteinuria in pregnancy through a mechanism largely indep endent of its anticoagulant action. AT III may thus be beneficial for the treatment of clinical symptoms of preeclampsia.