Interaction of glutamine and arginine on cerebrovascular reactivity to hypercapnia

Glutamine is purported to inhibit recycling of citrulline to arginine and t o limit nitric oxide release in vitro. However, vasoactive effects of gluta mine have not been clearly demonstrated in vivo. During hyperammonemia, imp aired cerebrovascular reactivity to CO2 is related to glutamine accumulatio n. We tested the hypotheses that 1) glutamine infusion in the absence of hy perammonemia impairs cerebrovascular CO2 reactivity and 2) arginine infusio n preserves CO2 reactivity during glutamine infusion and during hyperammone mia. Pentobarbital sodium-anesthetized rats were equipped with a closed cra nial 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 a t 3 h of glutamine infusion. Coinfusion of 2 mmol.kg(-1).h(-1) of L-arginin e with glutamine maintained the hypercapnic vasodilation at the control val ue. Infusion of ammonium acetate at a rate known to produce threefold incre ases in cortical tissue glutamine concentration resulted in no significant hypercapnic vasodilation. Coinfusion of arginine with ammonium acetate main tained hypercapnic vasodilation at 60% of the control value. Arginine infus ion did not augment hypercapnic vasodilation in a control group. We conclud e that glutamine modulates cerebrovascular CO2 reactivity in vivo. Glutamin e probably acts by limiting arginine availability because the vascular inhi bitory effect required >3 h to develop and because arginine infusion counte racted the vascular effect of both endogenously and exogenously produced in creases in glutamine.