Impaired release of tissue-type plasminogen activator (t-PA) from vascular endothelium in essential hypertension

Purpose. We recently demonstrated that local infusion of desmopressin (DDAVP) induces a massive release of t-PA from the forearm vascular bed in young healthy subjects. The aim of the present study was to investigate the capacity for acute t-PA release in patients with established essential hypertension. Methods. Seven non-smoking hypertensive (HT) males were studied 3 weeks after withdrawal of medication and compared to 6 healthy normotensive (NT) control subjects. DDAVP (7-21 -70ng/min) was infused in the brachial artery for 5 - 5 - 15 min. Forearm net release rates of t-PA were determined as the product of the venoarterial concentration gradient and local plasma flow. Results. DDAVP-induced release of t-PA antigen was markedly suppressed in the HT group compared to the NT group (ANOVA; p=0.0001). Average maximum release rates were 66 and 172 ng per min and L tissue in HT and NT subjects, respectively. Total amount of t-PA released in response to stimulation was on the average 1.490 ng (range 480 - 1.860) in the HT group, and 4,210 ng (range 3,170 8,730) in the NT group (p=0.003). In HT subjects, release of free t-PA was suppressed in a similar fashion. Forearm blood flow increased to the same extent in both groups. Conclusions. The capacity for acute t-PA release is markedly impaired in essential hypertension. This cannot be ascribed to deficient V2 receptor stimulation, since DDAVP-induced vasodilation was preserved. The findings indicate that the endothelial pool of t-PA available for acute release is reduced in hypertension, which might contribute to a defective local defense against arterial thrombosis.