Stimulation of nitric oxide synthesis and protective role of insulin in acute thrombosis in vivo

Administration of physiologic amounts of insulin in mice (200 mu units/g bo dy weight) resulted in 9 fold increase of basal nitric oxide level from 0.5 1+/-0.1224 nmol/ml (mean+/-SD, n=12) to 4.45+/-0.645 nmol/ml after 30min of the injection of the hormone. Since NO is a potent inhibitor of platelet a ggregation both in vitro and in vivo, we tested the possibility whether the administration of the hormone would result in the in vivo inhibition of th rombosis through the increase of NO level in the circulation. It was found that administration of insulin (200 mu units/g body weight) in mice protect ed >90%(p<0.00001, n=500) of these animals from death due to thrombosis in the coronary arteries induced by ADP injection in the heart. This effect of insulin in vivo was found to be directly related to the hormone induced in crease of NO level in the system. The thromboprotective effect of insulin c ould not be achieved by using either prostacyclin, a well known antithrombo tic agent or its stable probe prostaglandin E-1 instead of insulin. The eff icacy of insulin was neither related to the blood glucose level nor was the consequence of the hypoglycemic effect of the hormone. In contrast, inhibi tion of insulin induced increase of NO level resulted in the complete loss of the thromboprotective effect of the hormone. These results suggest that insulin besides being a hypoglycemic hormone could also be a potent antithr ombotic humoral factor.