Intracarotid infusion of the nitric oxide synthase inhibitor, L-NMMA, modestly decreases cerebral blood flow in human subjects
Background: The authors hypothesized that if nitric oxide (NO) was a determinant of background cerebrovascular tone, intracarotid infusion of N(G)-monomethyl-L-arginine (L-NMMA), a NO synthase (NOS) inhibitor, would decrease cerebral blood flow (CBF) and intracarotid L-arginine would reverse its effect. Methods: In angiographically normal cerebral hemispheres, after the initial dose-escalation studies (protocol 1), the authors determined the effect of intracarotid L-NMMA (50 mg/min for 5 min) on CBF and mean arterial pressure (MAP) over time (protocol 2). Changes in CBF and MAP were then determined at baseline, during L-NMMA infusion, and after L-NMMA during L-arginine infusion (protocol 3). To investigate effects of higher arterial blood concentrations of L-NMMA, changes in CBF and MAP were assessed at baseline and after a bolus dose of L-NMMA (250 mg/1 min), and vascular reactivity was tested by intracarotid verapamil (1 mg/min, protocol 4). CBF changes were also assessed during induced hypertension with intravenous phenylephrine (protocol 5). Results: Infusion of L-NMMA (50 mg/min for 5 min, n = 7, protocol 2) increased MAP by 17% (86 ± 8 to 100 ± 11 mmHg; P < 0.0001) and decreased CBF by 20% (45 ± 8 to 36 ± 6 ml · 100 g-1 · min-1; P < 0.005) for 10 min. Intracarotid L-arginine infusion after L-NMMA (protocol 3) reversed the effect of L-NMMA. Bolus L-NMMA (protocol 4) increased MAP by 20% (80 ± 11 to 96±13 mmHg; P < 0.005), but there was no significant decrease in CBF. Intracarotid verapamil increased CBF by 41% (44 ± 8 to 62 ± 9 ml · 100 g-1 · min-1; P < 0.005). Phenylephrine-induced hypertension increased MAP by 20% (79 ± 9 to 95 ± 6 mmHg; P = 0.001) but did not affect CBF. Conclusions: The results suggest that intracarotid L-NMMA modestly decreases CBF, and the background tone of cerebral resistance vessels may be relatively insensitive to NOS inhibition by the intraarterial route.
Angiography, Cerebrovascular resistance, sedation, vasodilator
Digital Object Identifier (DOI)
Joshi, Shailendra; Young, William L.; Duong, D. Hoang; Ostapkovich, Noeleen D.; Aagaard, Beverly D.; Hashimoto, Tomoki; and Pile-Spellman, John, "Intracarotid infusion of the nitric oxide synthase inhibitor, L-NMMA, modestly decreases cerebral blood flow in human subjects" (2000). Translational Neuroscience. 1680.