Disassociation of intrinsic and haemodynamic responses in stenotic arteries

Abstract

In stenotic arteries, constriction can decrease intraluminal pressure, which in turn can further decrease vessel size. Because of these pressure changes, the hypothesis that haemodynamic responses may be significantly different from intrinsic smooth muscle responses in stenotic arteries was tested. In rabbits (n = 16), one iliac artery was denuded (stenotic), and the other iliac artery was untouched (hypercholesterolaemic). The rabbits were placed on a 2% cholesterol diet for three weeks. Iliac arteries from these and normal (n = 8) rabbits were removed and studied as rings or perfused segments. In arterial rings, maximal isometric tension in response to noradrenaline was significantly (p < 0.05) greater in hypercholesterolaemic [0.59(SEM 0.03) x 10(6) dynes.cm-2] and normal arteries 0.63(0.04) compared with stenotic arteries [0.28(0.04)]. Normal [EC50 = 6.99(0.07), -log(M)] and hypercholesterolaemic [EC50 = 7.00(0.12)] rings were more sensitive (p < 0.05) to noradrenaline than stenotic rings [EC50 = 6.49(0.24)]. All arterial rings vasodilated in response to glyceryl trinitrate, and changes in isometric tension occurred over a 1000-fold change in noradrenaline or glyceryl trinitrate concentration. In normal and hypercholesterolaemic arteries, flow was unaltered even at the highest noradrenaline concentration. In stenotic arteries, noradrenaline decreased distal pressure from 76.9(5.4) to 24.3(7.3) mm Hg (p < 0.05) and flow from 17.9(1.6) to 6.4(1.8) ml.min-1 (p < 0.05). After noradrenaline decreased flow, glyceryl trinitrate did not always successfully vasodilate the stenotic arteries and thereby re-establish flow. Lastly, in stenotic arteries, most of the haemodynamic response occurred at one incremental dose of noradrenaline or glyceryl trinitrate. Fundamentally different haemodynamic responses occur in stenotic v normal and hypercholesterolaemic arteries. As the intrinsic smooth muscle responses (from the stenotic rings) are weaker, the augmented responses in whole stenotic segments are probably related to the intraluminal pressure changes.