Effect of Nitric Oxide Blockade on the Lower Limit of the Cortical Cerebral Autoregulation in Pentobarbital- Anaesthetized Rats

Abstract

The role of nitric oxide (NO) in cerebral autoregulation is controversial. The purpose of this study was to compare the effects on the lower limit of the cortical cerebral autoregulation of the inhibition of NO synthesis by N^ω-nitro-L-arginine (L-NNA) infusion to saline and phenylephrine in pentobarbital-anaesthetized rats. Variations of the cortical cerebral blood flow (CBF), the cortical cerebrovascular resistances, the mean arterial pressure and the lower limit of cerebral autoregulation were compared in three groups: a group pre-treated with L-NNA (n = 8), a group pretreated with saline (n = 8) and a group pretreated with phenylephrine (n = 5). The laser-Doppler flowmetry continuously measured CBF. Controlled haemorrhage was performed after the intravenous infusion of L-NNA, saline, or phenylephrine. The lower limit of cerebral autoregulation of each rat was computed by the least-squares method. The lower limit of cerebral autoregulation was significantly higher after L-NNA infusion (74 ± 5 mm Hg) than after saline (43 ± 3 mm Hg; p < 0.01) or phenylephrine infusions (52 ± 5 mm Hg; p < 0.05). In conclusion, the role of NO on the cerebral autoregulation has been controversial; our results confirm the hypothesis that NO exerts a significant role in maintaining the lower limit of cerebral autoregulation in pentobarbital-anaesthetized rats.

The Pharmacology of Nitric Oxide in the Peripheral Nervous System of Blood Vessels

“…These authors noted that cerebral blood flow in various superficial and deep brain regions was decreased by lowering of systemic blood pressure in rats treated with 30 mg/kg L-NMMA but not in untreated rats. Similar results were also reported in anesthetized rats (Preckel et al, 1996;Jones et al, 1999) and cats (Kobari et al, 1994), in which the role of NO in maintaining the lower limit of cerebral autoregulation was emphasized. Hardy et al (1999) have suggested that NO curtails the upper limit of cerebral autoregulation in anesthetized newborn pigs.…”

Cerebral Blood Flow Regulation by Nitric Oxide: Recent Advances

“…There is evidence supporting the idea that NO is involved in the physiological autoregulation of cerebral blood flow in rats (Tanaka et al, 1993;Preckel et al, 1996;Jones et al, 1999;Sugimoto et al, 2000), cats (Kobari et al, 1994), and newborn pigs (Hardy et al, 1999). NO synthesis exerted an important influence on the pressure-flow relationships of the internal and external carotid artery circulations, as L-NMMA increased input perfusion pressure at any given flow rate; however, in the presence of NO synthesis, hydraulic conductance increased rapidly with flow in the internal carotid artery, thereby stabilizing perfusion pressures over a wide range of flow rates, whereas this phe-NO AND CEREBRAL BLOOD FLOW nomenon was not evident in the external carotid artery territory (Ujiie et al, 2002).…”

L-arginine reactivity in cerebral vessels after severe traumatic brain injury

“…Experimental studies regarding the role of nitric oxide in pressure autoregulation are less clear. Most studies have suggested no role for nitric oxide in pressure autoregulation,38 but some suggest at least some role for nitric oxide 39,40…”