Pflügers Archiv : European journal of physiology
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The rostral ventrolateral medulla (RVLM) plays a pivotal role in regulating sympathetic vasomotor activity. The cardiac sympathetic afferent reflex (CSAR) contributes to the enhanced sympathetic outflow in chronic heart failure and hypertension. The aim of the present study was to determine whether angiotensin (Ang) II and Ang-(1-7) in the RVLM modulate the CSAR and sympathetic activity. ⋯ These results indicate that Ang-(1-7) is as effective as Ang II in sensitizing the CSAR and increasing sympathetic outflow. In contrast to Ang II, the effects of Ang-(1-7) are not mediated by AT(1) receptors but by Mas receptors. Mas receptors, but not the AT(1) receptors, in the RVLM are involved in the tonic control of the CSAR.
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The generation of action potentials in nociceptive neurons is accomplished by the tetrodotoxin-resistant (TTXr) Na+ channel Na(v)1.8. Following nerve injury, a redistribution of Na(v)1.8 from dorsal root ganglion (DRG) neurons into peripheral axons contributes to hyperexcitability and possibly to neuropathic pain. Na(v)1.8 has been reported to display a lower sensitivity to block by Na+ channel blockers as compared to TTX-sensitive (TTXs) Na(v) subunits. ⋯ The efficacy of lidocaine on neurons lacking Na(v)1.8 was further increased by cold temperatures, due to a synergistic hyperpolarizing shift of the slow inactivation of TTXs Na+ channels by lidocaine and cooling. Finally, the approximately 90% reduction of TTXr Na+ currents in injured neurons from mice with a peripheral nerve injury was accompanied with an enhanced tonic block by lidocaine. In conclusion, our data demonstrate that the expression of Na(v)1.8 in sensory neurons can confine the antinociceptive efficacy of lidocaine and other Na+ channel blockers employed for pain treatment.