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Am J Physiol Heart Circ Physiol 278: H1577-H1584, 2000;
0363-6135/00 $5.00
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Vol. 278, Issue 5, H1577-H1584, May 2000

Interaction of glutamine and arginine on cerebrovascular reactivity to hypercapnia

Toshiki Okada, Yukinaga Watanabe, Saul W. Brusilow, Richard J. Traystman, and Raymond C. Koehler

Department of Anesthesiology and Critical Care Medicine and Department of Pediatrics, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205

Glutamine is purported to inhibit recycling of citrulline to arginine and to limit nitric oxide release in vitro. However, vasoactive effects of glutamine have not been clearly demonstrated in vivo. During hyperammonemia, impaired cerebrovascular reactivity to CO2 is related to glutamine accumulation. We tested the hypotheses that 1) glutamine infusion in the absence of hyperammonemia impairs cerebrovascular CO2 reactivity and 2) arginine infusion preserves CO2 reactivity during glutamine infusion and during hyperammonemia. Pentobarbital sodium-anesthetized rats were equipped with a closed cranial window for measuring pial arteriolar diameter. Intravenous infusion of 3 mmol · kg-1 · h-1 of L-glutamine for 6 h produced threefold increases in plasma and cerebrospinal fluid concentrations. Dilation to hypercapnia was reduced by 45% compared with that of a time control group at 6 h but not at 3 h of glutamine infusion. Coinfusion of 2 mmol · kg-1 · h-1 of L-arginine with glutamine maintained the hypercapnic vasodilation at the control value. Infusion of ammonium acetate at a rate known to produce threefold increases in cortical tissue glutamine concentration resulted in no significant hypercapnic vasodilation. Coinfusion of arginine with ammonium acetate maintained hypercapnic vasodilation at 60% of the control value. Arginine infusion did not augment hypercapnic vasodilation in a control group. We conclude that glutamine modulates cerebrovascular CO2 reactivity in vivo. Glutamine probably acts by limiting arginine availability because the vascular inhibitory effect required >3 h to develop and because arginine infusion counteracted the vascular effect of both endogenously and exogenously produced increases in glutamine.

ammonia; carbon dioxide; cerebral blood vessels; nitric oxide; rat


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