Sympathetic nerve stimulation induces local endothelial Ca2+ signals to oppose vasoconstriction of mouse mesenteric arteries
| Autor: | Mark T. Nelson, Michael I. Kotlikoff, Thomas J. Heppner, Adrian D. Bonev, Lydia W. M. Nausch, Yvonne N. Tallini |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Sympathetic nervous system Sympathetic Nervous System Vascular smooth muscle Physiology Vascular Biology and Microcirculation Mice Transgenic Stimulation Biology Connexins Muscle Smooth Vascular Mice Physiology (medical) Internal medicine medicine Prazosin Animals Inositol 1 4 5-Trisphosphate Receptors Calcium Signaling Mesenteric arteries Feedback Physiological Ryanodine receptor Purinergic receptor Receptors Adrenergic alpha Intermediate-Conductance Calcium-Activated Potassium Channels Mesenteric Arteries Mice Inbred C57BL medicine.anatomical_structure Endocrinology Vasoconstriction Calcium Endothelium Vascular medicine.symptom Cardiology and Cardiovascular Medicine medicine.drug |
| Zdroj: | American Journal of Physiology-Heart and Circulatory Physiology. 302:H594-H602 |
| ISSN: | 1522-1539 0363-6135 |
| Popis: | It is generally accepted that the endothelium regulates vascular tone independent of the activity of the sympathetic nervous system. Here, we tested the hypothesis that the activation of sympathetic nerves engages the endothelium to oppose vasoconstriction. Local inositol 1,4,5-trisphosphate (IP3)-mediated Ca2+ signals (“pulsars”) in or near endothelial projections to vascular smooth muscle (VSM) were measured in an en face mouse mesenteric artery preparation. Electrical field stimulation of sympathetic nerves induced an increase in endothelial cell (EC) Ca2+ pulsars, recruiting new pulsar sites without affecting activity at existing sites. This increase in Ca2+ pulsars was blocked by bath application of the α-adrenergic receptor antagonist prazosin or by TTX but was unaffected by directly picospritzing the α-adrenergic receptor agonist phenylephrine onto the vascular endothelium, indicating that nerve-derived norepinephrine acted through α-adrenergic receptors on smooth muscle cells. Moreover, EC Ca2+ signaling was not blocked by inhibitors of purinergic receptors, ryanodine receptors, or voltage-dependent Ca2+ channels, suggesting a role for IP3, rather than Ca2+, in VSM-to-endothelium communication. Block of intermediate-conductance Ca2+-sensitive K+ channels, which have been shown to colocalize with IP3 receptors in endothelial projections to VSM, enhanced nerve-evoked constriction. Collectively, our results support the concept of a transcellular negative feedback module whereby sympathetic nerve stimulation elevates EC Ca2+ signals to oppose vasoconstriction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|