Autonomic Cardiovascular Control During a Novel Pharmacologic Alternative to Ganglionic Blockade

The purpose of this study was to compare ganglionic blockade with trimethaphan (TMP) and an alternative drug strategy using combined muscarinic antagonist (glycopyrrolate, GLY) and α ‐2 agonist (dexmedetomidine, DEX). Protocol 1 : incremental phenylephrine was administered during control and combined GLY‐DEX, or control and TMP on two control combined GLY and DEX or TMP infusion on two randomized days. Protocol 2 : muscle sympathetic nerve activity (MSNA) and the baroreflex MSNA relationship was determined before and after GLY–DEX. Blood pressure was higher with GLY–DEX (99±3 mm Hg) and lower with TMP (78±3 mm Hg) relative to control (GLY–DEX: 90±2 mm Hg; TMP: 91±2 mm Hg; P <0.05). Incremental phenylephrine increased pressure during GLY–DEX ( P <0.01 vs control) and TMP ( P <0.01 vs control) to a similar degree. Both GLY–DEX and TMP infusion inhibited norepinephrine release ( P <0.01 vs control). GLY–DEX inhibited baseline MSNA ( P <0.05) and baroreflex changes in MSNA ( P <0.01). We conclude that the GLY–DEX alternative drug strategy can be used as a reasonable alternative to pharmacologic ganglionic blockade to examine autonomic cardiovascular control. Clinical Pharmacology & Therapeutics (2008); 83 , 5, 692–701. doi: 10.1038/sj.clpt.6100326