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

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.