Platelet amplification of vasospasm

Abstract

Platelets may accentuate vasoconstriction in stenotic arteries capable of vasomotion. We examined the interaction of platelets, stenosis, and arterial vasoconstriction in normal and stenotic arteries with intact endothelium. Beagle carotid arteries (n = 38) were isolated, removed, and placed in an in vitro perfusion system. Platelet-rich plasma (PRP) or platelet-poor plasma (PPP) were perfused through the arteries under constant pressure (100 mmHg) and a fixed distal resistance. In intact arteries without a stenosis, angiotensin II (ANG II) decreased luminal diameter without altering flow during PRP perfusion. After creating an intraluminal stenosis, vasoconstriction produced by ANG II resulted in near total cessation of flow. During PRP perfusion, this effect was amplified, demonstrating suppression of flow at significantly (P less than 0.05) lower concentrations of ANG II (PRP, ED50 = 0.03 +/- 0.01 x 10(-8) M) compared with arteries perfused with PPP (PPP, ED50 = 2.7 +/- 0.8 x 10(-8) M). This accentuated vasoconstrictor response in the presence of platelets was not blocked by SKF 96148 (a thromboxane A2 antagonist) but was abolished by ketanserin (a 5-HT2-serotonergic blocker). This increased sensitivity to vasoconstriction was not due to significant platelet plugging inasmuch as no cyclic flow reductions were observed, aspirin (acetylsalicylic acid) did not prevent this accentuated vasoconstrictor response, and adventitial administration of nitroglycerin restored flow to baseline levels. These studies illustrate that 1) platelets amplify the effect of vasoconstrictors in stenotic arteries, 2) this amplification of vasoconstriction is primarily due to platelet release of serotonin, and 3) the amplification occurs in the absence of significant platelet plugging and endothelial damage.