Spinal cholinergic inhibition of the pressor response to skeletal muscle activation.

The purpose of this study was to delineate the role of the cholinergic pathway within the spinal cord in the reflex cardiovascular responses to muscle activity. Based on dose-response experiments, we microdialyzed a 0.1 mM solution of the acetylcholinesterase inhibitor neostigmine into the L7 level of the dorsal horn of anesthetized cats to determine its effects on the mean arterial blood pressure (MAP) and heart rate (HR) responses to static muscle contraction or passive stretch. The peak responses to 1-min contractions and stretches were reduced from control levels after 1 h of drug administration. In four experiments, the cardiovascular responses returned to control levels after a 2-h recovery period. Perfusion of the cholinergic receptor antagonist atropine accentuated the peak MAP response to muscle contraction. By contrast, atropine administration had no effect on the peak MAP adjustment to passive muscle stretch. These data support the hypothesis that increased acetylcholine (ACh) concentrations in the spinal cord inhibit the reflex cardiovascular responses to static muscle contraction. Further, the results suggest that the spinal cholinergic system is activated by metabolic changes in skeletal muscle, but likely unaffected by mechanical muscle changes.

Static muscle contraction elicits a baroreflex-dependent increase in glutamate concentration in the ventrolateral medulla.

In anesthetized cats, static contraction of the hindlimb reflexly increases mean arterial pressure (MAP). This cardiovascular adjustment is reduced by the arterial baroreflex. Both of these reflex responses are mediated through activation of ventrolateral medullary (VLM) regions. We tested the hypothesis that the concentration of glutamate (Glu) increases in the caudal ventrolateral medulla (cVLM) during static hindlimb contractions in anesthetized cats, and that barodenervation reduces this elevation in Glu levels. Static contractions of the triceps surae muscle of one hindlimb were evoked by electrical stimulation of the peripheral ends of cut L7 and S1 ventral roots. After the insertion of the microdialysis probes and a 3-h recovery period, a 2-min static contraction increased MAP by 47 +/- 7 mmHg. The concentration of Glu increased from 606 +/- 189 to 1042 +/- 228 nM. These results were repeatable in that Glu, as well as MAP, rose by a similar amount in two subsequent contractions. By contrast, in a subset of cats paralyzed prior to the third contraction, neither MAP nor Glu were significantly increased over baseline levels during the third stimulation period. In a third group of cats, hindlimb contraction increased MAP and Glu levels. However, the Glu release was attenuated in subsequent contractions after these cats were barodenervated. During the same periods of stimulation, the denervation accentuated the rise in MAP. These data demonstrate that static contraction of the hindlimb increases the extracellular concentration of Glu in the cVLM. Further, our study implicates this neurotransmitter in the baroreflex mediated reduction of the pressor reflex response to static muscle contraction.