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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Hindbrain chemical mediators of reflex-induced inhibition of gastric tone produced by esophageal distension and intravenous nicotine

Departments of ¹Pharmacology and ²Medicine (Endocrinology), Georgetown University Medical Center, Washington, District of Columbia

Submitted 6 January 2005 ; accepted in final form 19 July 2005

The purpose of this study was to activate a vagovagal reflex by using esophageal distension and nicotine and test whether hindbrain nitric oxide and norepinephrine are involved in this reflex function. We used double-labeling immunocytochemical methods to determine whether esophageal distension (and nicotine) activates c-Fos expression in nitrergic and noradrenergic neurons in the nucleus tractus solitarii (NTS). We also studied c-Fos expression in the dorsal motor nucleus of the vagus (DMV) neurons projecting to the periphery. Esophageal distension caused 19.7 ± 2.3% of the noradrenergic NTS neurons located 0.60 mm rostral to the calamus scriptorius (CS) to be activated but had little effect on c-Fos in DMV neurons. Intravenous administration of nicotine caused 19.7 ± 4.2% of the noradrenergic NTS neurons 0.90 mm rostral to CS to be activated and, as reported previously, had no effect on c-Fos expression in DMV neurons. To determine whether norepinephrine and nitric oxide were central mediators of esophageal distension-induced decrease in intragastric pressure (balloon recording), N^G-nitro-L-arginine methyl ester microinjected into the NTS (n = 5), but not into the DMV, blocked the vagovagal reflex. Conversely, ₂-adrenergic blockers microinjected into the DMV (n = 7), but not into the NTS, blocked the vagovagal reflex. These data, in combination with our earlier pharmacological microinjection data with nicotine, indicate that both esophageal distension and nicotine produce nitric oxide in the NTS, which then activates noradrenergic neurons that terminate on and inhibit DMV neurons.

vagus nerves; dorsal motor nucleus of the vagus; medial subnucleus of the tractus solitarii; ₂-adrenoreceptor; esophageal distension; c-Fos; nitric oxide synthase; central nervous system

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