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 mm Hg) 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 mm Hg, HEX + PE: 103+/-3 mm Hg) 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.
Collister
J P
JP
Department of Veterinary PathoBiology, University of Minnesota, St. Paul, MN 55108, USA.
Osborn
J W
JW
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000818:Animals; D001340:Autonomic Nerve Block; D017704:Baroreflex / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D005730:Ganglionic Blockers / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium / Q000494:pharmacology*; D007262:Infusions, Intravenous; D008297:Male; D010656:Phenylephrine / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012964:Sodium / Q000378:metabolism; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D005730:Ganglionic Blockers; D010656:Phenylephrine; D018738:Hexamethonium; D004246:Dimethylphenylpiperazinium Iodide; D012964:Sodium; D012083:Renin