Direct Vascular Effects of Protease-Activated Receptor Type 1 Agonism In Vivo in Humans

Abstract

Background-Protease-activated receptor type 1 (PAR-1) has been proposed as the principal thrombin receptor in humans, although its actions in vivo have not been defined. The aim of the present study was to determine the direct vascular actions of PAR-1 agonism in humans.

Dabigatran and Thrombin Modulate Electrophysiological Characteristics of Pulmonary Vein and Left Atrium

“…PAR1 agonists were also demonstrated to have inconsistent vessel effects with venous constriction and arterial dilation in humans. 30 Because distribution of NOS isoforms may differ between the atrium and PVs, it is possible that different activations of distinct cGMP-dependent and cGMP-independent signaling pathways may result in the different effects of thrombin on diastolic tensions between PV and LA. 31 Thrombin's reduction of LA contractile force may have resulted from mixed effects of vagal stimulation and the compartmentalized distribution of NOS isoforms and NO-related congeners.…”

Role of the Endothelium in the Vascular Effects of the Thrombin Receptor (Protease-Activated Receptor Type 1) in Humans

“…Using the short peptide mimetic SFLLRN, we have recently described the in vivo effects of PAR-1 activation in platelets, endothelium and vascular smooth muscle in man. For the first time, we were able to show that PAR-1 activation has unique and contrasting effects in the human vasculature including arterial dilation, venous constriction, platelet activation, and tissue-type plasminogen activator (t-PA) release (9). Given the central role of thrombin in the pathophysiology of cardiovascular disease, it is important to establish the mechanisms of these PAR-1-mediated effects and, in particular, the role of the endothelium.…”

“…Supine heart rate and blood pressure were monitored at intervals throughout each study using a semiautomated noninvasive oscillometric sphygmomanometer. Tirofiban (1.25 g/min) was coinfused during the studies to inhibit potential PAR-1 activation-induced platelet aggregation in vivo (9). This dose of tirofiban does not affect platelet-monocyte binding, forearm blood flow, or baseline concentration of t-PA (9).…”

Iliac Venous Stenting

“…PAR-1 agonists have been shown to promote platelet activation, venous constriction, arterial dilatation, and tPA release both in vitro and in vivo. 24,25 Further studies with a selective platelet PAR-1 antagonist would aid in elucidating the relative role of thrombin-mediated platelet activation compared with fibrin formation in thrombus generation in this model. 26,27 There are several study limitations which should be acknowledged.…”