DISPARATE EFFECTS OF THROMBIN RECEPTOR ACTIVATING PEPTIDE ON PLATELETS AND PERIPHERAL VASCULATURE IN RATS

The hemodynamic and platelet effects of the thrombin receptor activati ng peptide SFLLRN (TRAP) were evaluated in rats. TRAP failed to aggreg ate rat platelets in vitro (platelet rich plasma) or in vivo in the pu lmonary microcirculation. In contrast, TRAP aggregated washed human pl atelets. Intravenous injection of TRAP (1 mg/kg) in inactin-anesthetiz ed rats produced a biphasic response in blood pressure characterized b y an initial depressor response (-25 +/- 3 mmHg for 15-30 s) followed by a pronounced presser response (50 +/- 7 mmHg for 2-3 min). This inc rease in blood pressure can be attributed to increases in total periph eral resistance since cardiac output remained unchanged. Further, only the presser responses were observed in pithed rats suggesting a direc t effect of TRAP in causing smooth muscle contraction. Consequently, r at platelets differ from human platelets in that they are resistant to TRAP whereas fat vasculature is highly sensitive to TRAP. These obser vations suggest that while the thrombin receptors on rat vasculature m ay be similar to those on human platelets, the receptors and/or the co upling mechanisms in rat platelets appear different from human platele ts. (C) 1998 Elsevier Science B.V. All rights reserved.