The fibrinolytic system attenuates vascular tone: effects of @entity2435 ( XXXX ) and aminocaproic acid on renal microcirculation.

@entity8 @entity28700 @entity2630 @entity141 @entity929 @entity930 @entity2647 @entity2435 @entity35
1. The renal medulla is a major source of plasminogen activators (PA), recently shown to induce vasodilation in vitro. Treatment with PA inhibitors has been associated with @entity8 , suggesting compromised renal microvasculature. We investigated the impact of the PA inhibitor @entity929 ( @entity930 ) upon vascular tone in vitro, and studied the effect of both @entity2435 and @entity930 upon intrarenal hemodynamics in vivo. 2. In vitro experiments were carried out in isolated aortic rings and with cultured vascular smooth muscle cells. Studies of renal microcirculation and morphology were conducted in anesthetized @entity35 . 3. In isolated aortic rings, @entity930 (but not the other inhibitors of the fibrinolytic system @entity2630 or @entity28700 ) reduced the half-maximal effective concentration of @entity2647 (PE) required to induce contraction (from 32 nm in control solution to 2 and 0.1 nm at @entity930 concentrations of 1 and 10 microm, respectively). Using reteplase (retavase) in the same model, we also provide evidence that the vasoactivity of @entity2435 is in part kringle-dependent. In cultured vascular smooth muscle cells, @entity141 internalization following PE was enhanced by @entity930 , and retarded by @entity2435 . 4. In anesthetized @entity35 , @entity930 (150 mg x kg(-1)) did not affect systemic blood pressure, total renal or cortical blood flow. However, the outer medullary blood flow declined 12+/-2% below the baseline (P<0.03). By contrast, @entity2435 (2 mg x kg(-1)), transiently increased outer medullary blood flow by 8+/-5% (P<0.02). Fibrin microthrombi were not found within the renal microvasculature in @entity930 -treated animals. 5. In conclusion, both fibrinolytic and antifibrinolytic agents modulate medullary renal blood flow with reciprocal effects of vasodilation (PA) and vasoconstriction ( @entity930 ). In vitro studies suggest that these hemodynamic responses are related to direct modulation of the vascular tone.
