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Dominance of flow‐mediated constriction over flow‐mediated dilatation in the rat carotid artery
Author(s) -
Craig John,
Martin William
Publication year - 2012
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.2012.02006.x
Subject(s) - constriction , medicine , myograph , common carotid artery , cardiology , vasodilation , anesthesia , chemistry , carotid arteries
BACKGROUND AND PURPOSE The shearing forces generated by flow generally evoke dilatation in systemic vessels but constriction in the cerebral circulation. The aim of this study was to determine the effects of flow on the conduit artery delivering blood to the brain in the rat, that is, the carotid artery. EXPERIMENTAL APPROACH Carotid artery segments were mounted in a pressure myograph and pressurized to 100 mmHg. Changes in vessel diameter to flow (0.5–10 mL·min −1 for 2–10 min) at constant pressure were then measured using a video dimension analyser. KEY RESULTS Following the induction of tone, the onset of flow evoked a transient dilatation followed by a powerful constriction that was sustained until the termination of flow. Endothelial denudation or treatment with indomethacin, N G ‐nitro‐L‐arginine methyl ester, or the combination of apamin and TRAM−34 showed that the initial flow‐mediated dilatation arose from the combined actions of endothelium‐derived NO and endothelium‐derived hyperpolarizing factor (EDHF). The flow‐mediated constriction, which increased in magnitude with increasing flow rate and duration of flow, was also endothelium dependent, but was unaffected by treatment with superoxide dismutase, BQ‐123, indomethacin, HET0016 or carbenoxolone. Flow‐mediated constriction therefore appeared not to involve superoxide anion, endothelin‐1, a COX product, 20‐HETE or gap‐junctional communication. CONCLUSIONS AND IMPLICATIONS Although a weak, transient flow‐mediated dilatation is observed in the rat carotid artery, the dominant response to flow is a powerful and sustained constriction. Whether this flow‐mediated constriction in the carotid artery serves as an extracranial mechanism to regulate cerebral blood flow remains to be determined.