To investigate the acute effects of insulin on the fibrinolytic system in essential hypertension (EH), plasma plasminogen activator inhibitor 1 (PAI-1), which is a major anti-fibrinolytic substance, tissue plasminogen activator (tPA), thrombomodulin (TM), triglycerides (TG), and free fatty acids (FFA) were measured in 14 middle-aged, non-obese patients with EH and 6 age-matched control subjects at a hyperglycemic, euglycemic glucose clamp before and after a 2 hour-insulin infusion.
Serum insulin level during the clamp was 78-186μU/ml and blood glucose was maintained at 80-105mg/dl. The glucose infusion rate was significantly less in the patients (5.3±1.7 mg/kg/min) than in the controls (9.1±1.3mg/kg/min). During the clamp, plasma PAI-1 concentration did not significantly change in the patients whereas it was significantly lowered in the controls (by 42%): abnormality of regulation of PAI-1 is related to the degree of insulin resistance as indexed by lower glucose infusion rate in some of them. There was no suppression of tPA and TM both in the patients and controls. In contrast, TG and FFA levels were significantly suppressed by the insulin infusion in both groups.
We conclude that insulin acutely suppresses serum TG and FFA, but not plasma PAI-1 in patients with EH, implying that the acute effects of insulin on the lipids and PAI-1 are independent of each other. The findings suggest that the abnormal regulation of PAI-1, but not lipid, exists in patients with EH. This abnormality may well be related to the initiation and/or evolution of vascular complications in EH.