Unlike thrombin, protein C and activated protein C do not affect vascular tone

Because plasma levels of protein C (PC) or activated protein C (APC) are al tered in certain diseases associated with vascular dysfunction, and APC has therapeutic potential in preventing microvascular coagulation in severe se psis, potential vascular effects of PC and APC were compared to those of th e vasoactive peptide, thrombin. Thrombin was a more potent relaxant agonist than contractile agonist in aorta. Unlike thrombin, cumulatively administe red APC (10(-9)-10(-7) M) did not exert vascular effects in rat or rabbit a orta. Noncumulative challenge of PC (10(-7) M) and APC (8 X 10(-8) M) also did not contract rat or rabbit aortae, either with or without endothelium. Likewise, the same concentrations of PC and APC also did not relax norepine phrine-induced (10(-7) M) vascular tone in either rat or rabbit aortae. Thu s, in contrast to thrombin, PC and APC failed to modulate vascular tone, su ggesting that the therapeutic use of APC is unlikely to be accompanied by a lly direct effects on vascular motility. (C) 2000 Published by Elsevier Sci ence Inc.