Abstract 469: Intra-vital FRET Imaging Reveals Basal α-adrenergic Dominated Tone in Mouse Femoral Conduit Arteries
Enhanced vascular tone is always observed and responsible for the blood pressure elevation in hypertension. The cellular mechanisms that control vascular tone in vivo, particularly in hypertension, however, are not known with certainty. Here, using intra-vital FRET imaging in smooth muscle-specific exogenous myosin light chain kinase biosensor mice, we aimed to study the mechanism(s) that control the basal tone in femoral conduit arteries under normal physiological conditions (Zhang et al., Am J Physiol 299: H946-56, 2010). Quantification of arterial [Ca2+]i and diameter revealed that, in the basal state, femoral arteries exhibit 33 ± 3% tone (percentage of passive diameter, 400 ± 30 μm, obtained in Ca2+-free solution), [Ca2+]i is 233 ± 18 nM. Acute ganglionic blockade with hexamethonium (30 mg/kg wt, i.p.) lowered [Ca2+]i by 216 ± 23 nM, reduced the basal tone by 67 ± 12%, and decreased mean blood pressure by ∼60 mm Hg, suggesting a dominant autonomic/sympathetic control of the basal tone. To assess contribution of the major sympathetic neurotransmitters, noradrenaline (NE), ATP and neuropeptide Y (NPY), to the basal tone in vivo, respective agonists and antagonists were applied locally to segments of exposed arteries. Prazosin (0.01-3 μM), an α1 adrenoceptor blocker, dose-dependently decreased [Ca2+]i and basal tone, without affecting blood pressure or heart rate. Yohimbine (0.1-1 μM), an α2 adrenoceptor blocker, reduced tone with negligible effect on [Ca2+]i (n = 4). These effects were abolished by chemical destruction of sympathetic nerves locally with hydroxydopamine (2 mM), indicating that the basal tone is maintained by neurotransmitters released from nerve terminals, but not activated by circulating neurotransmitter-like factors. Suramin (a purinergic receptor blocker), BIBO 3304 (a NPY receptor blocker), and losartan (angiotensin II AT1 receptor blocker), had negligible effect on either [Ca2+]i or diameter. Our results indicate that femoral arteries possess basal neurogenic tone, primarily α-adrenergic, under normal physiological condition. This basal tone observed in femoral arteries could be particularly useful for assessing sympathetic nerve activity in disease models, such as hypertension.
- © 2012 by American Heart Association, Inc.