NITRIC-OXIDE MEDIATION OF CHEMOREGULATION BUT NOT AUTOREGULATION OF CEREBRAL BLOOD-FLOW IN PRIMATES

The authors sought to develop a model for assessing in vivo regulation of cerebral vasoregulation by nitric oxide (NO), originally described as endothelial-derived relaxing factor, and to use this model to esta blish the role of NO in the regulation of cerebral blood flow (CBE) in primates. By using regional intraarterial perfusion, the function of NO in cerebral vasoregulation was examined without producing confoundi ng systemic physiological effects. Issues examined were: whether resti ng vasomotor tone requires NO; whether NO mediates vasodilation during chemoregulation and autoregulation of CBF; and whether there is a rel ationship between the degree of hypercapnia and hypotension and NO pro duction. Twelve anesthetized (0.5% isoflurane) cynomolgus monkeys were monitored continuously for cortical CBF, PaCO2, and mean arterial pre ssure (MAP), which were systematically altered to provide control and experi mental curves of chemoregulation (CBF vs. PaCO2) and autoregula tion (CBF vs. MAP) during continuous intracarotid infusion of 1) salin e and 2) an NO synthase inhibitor (NOSI), either L-n-monomethyl argini ne or nitro L-arginine. During basal conditions (PaCO2 of 38-42 mm Hg) NOSI infusion of internal carotid artery (ICA) reduced cortical CBF f rom 62 (saline) to 53 ml/100 g/per minute (p < 0.01), although there w as no effect on MAP. Increased CBF in response to hypercapnia was comp letely blocked by ICA NOSI. The difference in regional (r)CBF between TCA saline and NOSI infusion increased linearly with PaCO2 when PaCO2 was greater than 40 mm Hg, indicating a graded relationship of NO prod uction, increasing PaCO2, and increasing CBF. Diminution of CBF with N OSI infusion was reversed by simultaneous ICA infusion of L-arginine, indicating a direct role of NO synthesis in the chemoregulation of CBF . Hypotension and hypertension were induced with trimethaphan camsylat e (Arfonad) and phenylephrine at constant PaCO2 (40 +/- 1 mm Hg). Auto regulation in response to changes in MAP from 50 to 140 mm Hg was unaf fected by ICA infusion of NOSI. In primates, cerebral vascular tone is modulated in vivo by NO; continuous release of NO is necessary to mai ntain homeostatic cerebral vasodilation; vasodilation during chemoregu lation of CBF is mediated directly by NO production; autoregulatory va sodilation with hypotension is not mediated by NO; and increasing PaCO 2 induces increased NO production.