The chronic infusion of hexamethonium and phenylephrine to effectively clamp sympathetic vasomotor tone: A novel approach

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There are several ways to assess the sympathetic nervous system (i.e., nerve recording, sympathectomy, etc.), each of which has its own limitations. The present study was conducted to establish a standard, testable chronic ganglionic blockade protocol with a fixed level of adrenergic vasomotor tone. Rats were instrumented with radio telemetry pressure transducers and venous catheters for continuous measurement of arterial pressure and infusion of pharmacologic agents, respectively. After 3 days of control measurements, rats were infused for 9 days with a continuous dose of the ganglionic blocking agent, hexamethonium and the alpha-adrenergic agonist, phenylephrine. In this way, sympathetic tone was effectively 'clamped,' which maintained a normal level of arterial pressure. Control pressure between hexamethonium + phenylephrine (HEX + PE) treated rats (101 ± 2 mmHg) and saline (VEHICLE) treated rats (101 ± 2 mmHg) was not different. By day 9 of the infusion, there was no difference in arterial pressure between groups (VEHICLE: 101 ± 3 mmHg, HEX + PE: 103 ± 3 mmHg) or from the control period, although heart rate was significantly less in HEX+ PE rats (VEHICLE: 406 ± 9 beats/min vs. HEX + PE: 343 ± 6 beats/min). The effectiveness of this technique was validated by measuring cardiac baroreceptor reflex sensitivity, as well as the pressor response to the direct ganglionic stimulating agent, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP). Compared to VEHICLE rats, HEX + PE rats showed no tachycardic response to depressor stimuli and an absence of a pressor response to DMPP. We conclude that this protocol is a useful technique to chronically, yet reversibly, block the sympathetic nervous system in experimental settings. (C) 2000 Elsevier Science Inc.

Original languageEnglish (US)
Pages (from-to)135-147
Number of pages13
JournalJournal of Pharmacological and Toxicological Methods
Issue number3
StatePublished - Nov 1999

Bibliographical note

Funding Information:
This study was supported by National Heart, Lung, and Blood Institute grant HL-03790-02.


  • Arterial pressure
  • Autonomic nervous system
  • Ganglionic blockade


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