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Effects of medullary administration of a nitric oxide precursor on cardiovascular responses and neurotransmission during static exercise following ischemic stroke

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We have reported that in rats with a 90 min left middle cerebral artery occlusion (MCAO) and 24 h reperfusion, pressor responses during muscle contractions were attenuated, as were glutamate concentrations in the left rostral ventrolateral medulla (RVLM) and left caudal VLM (CVLM), but gamma-aminobutyric acid (GABA) levels increased in left RVLM and CVLM. This study determined the effects of l-arginine, a nitric oxide (NO) precursor, within the RVLM and (or) CVLM on cardiovascular activity and glutamate/GABA levels during static exercise in left-sided MCAO rats. Microdialysis of l-arginine into left RVLM had a greater attenuation of cardiovascular responses, a larger decrease in glutamate, and a significant increase in GABA levels during muscle contractions in stroke rats. Administration of N G-monomethyl-l-arginine, an NO-synthase inhibitor, reversed the effects. In contrast, l-arginine administration into left CVLM evoked a greater potentiation of cardiovascular responses, increased glutamate, and decreased GABA levels during contractions in stroked rats. However, l-arginine administration into both left RVLM and left CVLM elicited responses similar to its infusion into the left RVLM. These results suggest that NO within the RVLM and CVLM modulates cardiovascular responses and glutamate/GABA neurotransmission during static exercise following stroke, and that a RVLM–NO mechanism has a dominant effect in the medullary regulation of cardiovascular function.
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Keywords: GABA; attaque; blood pressure; caudal ventrolateral medulla; glutamate; microdialyse; microdialysis; pression sanguine; rostral ventrolateral medulla; stroke; zone médullaire ventro-latérale caudale; zone médullaire ventro-latérale rostrale

Document Type: Research Article

Affiliations: 1: Department of Pharmacy Practice, Chulalongkorn University, Bangkok, Thailand. 2: Department of Pharmaceutical Sciences, Massachusetts College of Pharmacy and Health Sciences, Boston, MA 02115, USA. 3: Department of Pharmaceutical Sciences, South College School of Pharmacy, 400 Goody’s Lane, Knoxville, TN 37922, USA.

Publication date: January 1, 2013

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