Alternative to ganglionic blockade with anticholinergic and alpha-2 receptor agents

The ganglionic blocking agent trimethaphan (TMP) is no longer produced. Therefore, a need exists for alternative pharmacological approaches to investigate baroreflex control of the circulation. The aim of the present study was to examine baroreflex-mediated cardiovascular responses during the administration of a muscarinic receptor antagonist (glycopyrrolate; Gly) and a selective alpha-2 receptor agonist (dexmedetomidine; Dex) and to compare responses to ganglionic blockade with TMP. We hypothesized that combined Gly-Dex would inhibit the baroreflex similar to TMP. Ten volunteers participated in two study days and were instrumented with pulse oximeter, nasal cannula, ECG, continuous blood pressure monitoring (Finapres), and I.V. catheter for drug infusions. Each study day consisted of a control condition followed by either combined Gly-Dex or TMP on alternating days. A Valsalva maneuver was performed under each condition with every subject and six subjects received bolus phenylephrine (25 μg) during Gly-Dex and TMP. Combined Gly-Dex increased (P < 0.05) blood pressure (99 ± 4 mmHg) and heart rate (99 ± 3 bpm) relative to control condition (BP: 90 ± 2 mmHg; HR: 64 ± 3 bpm) and TMP infusion decreased (P < 0.05) blood pressure (79 ± 3 mmHg) while increasing heart rate (88 ± 3 bpm). Valsalva maneuver elicited a persistent drop in arterial pressure (no phase IIb recovery) with the absence of a phase IV overshoot during both Gly-Dex and TMP conditions. Phenylephrine increased systolic pressure 34 ± 4 mmHg under Gly-Dex and 23 ± 3 mmHg with TMP (P < 0.05). Heart rate only decreased 1 ± 2 bpm during Gly-Dex and 1 ± 1 bpm with TMP. Taken together, our results suggest that Gly-Dex is a reasonable alternative to TMP for baroreflex inhibition.