Continuous flow augments reactivity of rabbit carotid artery by reducing bioavailability of NO despite an increase in release of EDHF

Abstract

Experiments were designed to investigate the influence of steady flow and pressure on endothelial function in the rabbit carotid artery. Increases and decreases in isometric force were compared in static rings and perfused (5 or 50 ml/min) segments of the same arteries in the presence and absence of endothelium. The alpha(1)-adrenoceptor agonist phenylephrine and the muscarinic agonist acetylcholine were applied as vasoconstrictor and vasodilator stimuli, respectively. Continuous flow (5 and 50 ml/min) reduced the cGMP content and shifted the concentration-response curve to phenylephrine to the left compared with nonperfused static rings. Removal of the endothelium abolished the differences in cGMP content and the sensitivity to phenylephrine between static rings and perfused segments. No difference in sensitivity to phenylephrine was observed in tissues treated with N(omega)-nitro-l-arginine methyl ester (l-NAME). Acetylcholine-evoked relaxations were increased in perfused segments. l-NAME nearly abolished the acetylcholine-evoked relaxation in static rings, whereas about one-half of the relaxation remained in segments exposed to flow. This remnant relaxation was blocked by inhibition of endothelial small- and intermediate-conductance calcium-activated potassium channels by apamin plus 1-[(2-chlorophenyl)diphenylmethyl]-1H-pyrazole (TRAM-34). These experiments demonstrate that continuous flow increases the constriction evoked by alpha(1)-adrenergic activation in the rabbit carotid artery through a reduced influence of basally released endothelial NO and, furthermore, that luminal flow unmasks an ability of the endothelium to release a non-NO, noncyclooxygenase vasodilator, presumably endothelium-derived hyperpolarizing factor.

Introduction of a Rabbit Carotid Artery Model for Sonothrombolysis Research

“…These requirements might include (a) a vessel size comparable to a M1 or M2 segment of a human middle cerebral artery (MCA) [26, 27], (b) a thrombus size/volume comparable to what can be expected in proximal M1 or M2 occlusions, (c) a bifurcation to mimic MCA branching, a preferred location for embolic occlusions, (d) the possibility to mimic a human transcranial insonation, mainly to account for appropriate acoustic signal absorption, (e) the ability to monitor flow and clot mechanics, preferably at any given timepoint before, after, or during the procedure, and (f) perhaps to provide the possibility to introduce actual human thrombi to achieve vessel occlusion.…”