IMPAIRED ENDOGENOUS FIBRINOLYTIC CAPACITY IN PREHYPERTENSIVE MEN

Prehypertension (BP 120–139/80–89 mmHg) is associated with an increased risk for future atherothrombotic events. Although the mechanisms underlying this elevated risk are not completely understood, one possibility is that prehypertension is associated with impaired endothelial fibrinolytic capacity. We tested the hypothesis that vascular endothelial release of t-PA is impaired in prehypertensive men. Net endothelial release of t-PA was determined, in vivo, in response to intrabrachial infusions of bradykinin (12.5, 25, 50 ng/100 mL tissue/min) and sodium nitroprusside at (1.0, 2.0, 4.0 µg/100 mL tissue/min) in 42 middle-age and older men: 16 normotensive (BP range: 100–119/57–79 mmHg); 16 prehypertensive (BP range: 120–139/76–89 mmHg); and 10 hypertensive (BP range: 140–150/74–100 mmHg). Net release of t-PA antigen was ~25% lower (P < 0.05) in the prehypertensive (−0.9 ± 0.8 to 42.4 ± 5.3 ng/100 mL tissue/min) compared with the normotensive (0.5 ± 1.0 to 53.9 ± 6.5 ng/100 mL tissue/min) men. There was no significant difference in t-PA release between the hypertensive (−1.8±1.6 to 40.8±6.6 ng/100 mL tissue/min) and prehypertensive groups. Sodium nitroprusside did not significantly alter t-PA release in any group. These data indicate that endothelial t-PA release is diminished in prehypertensive men. Further, the level of impairment in t-PA release seen with clinical hypertension is already apparent in the prehypertensive state. Impaired endothelial fibrinolytic function may underlie the increased atherothrombotic risk associated with blood pressure in the prehypertensive range.