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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

The sympathoinhibitory effects of systemic cholecystokinin are dependent on neurons in the caudal ventrolateral medulla in the rat

University of Melbourne, Department of Medicine, Clinical Pharmacology and Therapeutics Unit, Austin Health, Heidelberg, Victoria, Australia

Submitted 11 May 2006 ; accepted in final form 14 June 2006

The gastrointestinal hormone CCK inhibits a subset of presympathetic neurons in the rostroventrolateral medulla (RVLM) that may be responsible for driving the sympathetic vasomotor outflow to the gastrointestinal circulation. We tested the hypothesis that the central neurocircuitry of this novel sympathoinhibitory reflex involves a relay in the caudal ventrolateral medullary (CVLM) depressor area. Blood pressure and greater splanchnic sympathetic nerve discharge (SSND) or lumbar sympathetic nerve discharge (LSND) were monitored in anesthetised, paralyzed male Sprague-Dawley rats. The effects of phenylephrine (PE, 10 µg/kg iv; baroreflex activation), phenylbiguanide (PBG, 10 µg/kg iv; von Bezold-Jarisch reflex) and CCK (4 or 8 µg/kg iv) on SSND or LSND, were tested before and after bilateral injection of 50–100 nl of the GABA_A agonist muscimol (1.75 mM; n = 6, SSND; n = 7, LSND) or the excitatory amino acid antagonist kynurenate (55 mM; n = 7, SSND) into the CVLM. PE and PBG elicited splanchnic and lumbar sympathoinhibitory responses that were abolished by bilateral muscimol or kynurenate injection into the CVLM. Similarly, the inhibitory effect of CCK on SSND was abolished after neuronal inhibition within the CVLM. In contrast, CCK-evoked lumbar sympathoexcitation was accentuated following bilateral CVLM inhibition. In control experiments (n = 7), these agents were injected outside the CVLM and had no effect on splanchnic sympathoinhibitory responses to PE, PBG, and CCK. In conclusion, neurons in the CVLM are necessary for the splanchnic but not lumbar sympathetic vasomotor reflex response to CCK. This strengthens the view that subpopulations of RVLM neurons supply sympathetic vasomotor outflow to specific vascular territories.

splanchnic sympathetic nerve; lumbar sympathetic nerve; cholecystokinin; reflex; rat

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