Possible role of nitric oxide in autoregulatory response in rat intracerebral arterioles

OBJECTIVE: Cerebral autoregulation is an important regulatory mechanism that maintains a constant cerebral blood flow over a wide range of perfusion pressures. The goal of this study was to determine whether nitric oxide contributes to the autoregulatory response of cerebral arterioles to altered transmural pressure (TMP). METHODS: Seventy-nine intraparenchymal arterioles (53.6 ± 3.5 μm mean diameter) isolated from rats were cannulated with micropipettes and pressurized at a TMP of 60 mm Hg (control pressure). Vessel diameters were monitored continuously using a video dimensional analyzer. The autoregulatory diameter responses to varying intraluminal pressures were observed in the presence and absence of a nitric oxide synthase inhibitor, N(G)-monomethyl-L-arginine (L-NMMA). The effect of L-NMMA-induced constriction on autoregulatory response also was compared with responses after prostaglandin F(2α) and alkalosis-induced constrictions. RESULTS: Autoregulatory responses were observed over a range from 10 to 90 mm Hg of TMP. Treatment with 10^-4 mol/L L-NMMA constricted arterioles and inhibited the autoregulatory vasodilation to TMP reductions from 60 mm Hg to 10 or 30 mm Hg. In L-NMMA-treated arterioles, elevation in TMP from 60 to 90 mm Hg caused an autoregulatory vasoconstriction. Treatment with alkaline pH 7.65 constricted arterioles to a similar degree as that induced by L-NMMA at 60 mm Hg, and under these conditions, the autoregulatory response remained intact. Arterioles severely constricted with prostaglandin F(2α) showed no significant autoregulatory response. CONCLUSION: These results suggest that 1) vascular nitric oxide release increases in response to a decrease in TMP from 60 mm Hg, thereby contributing to the autoregulatory vasodilation intrinsic to the vessel during hypotension, 2) arteriolar nitric oxide appears not to be involved in the autoregulatory vasoconstriction induced by elevating TMP from 60 to 90 mm Hg, and 3) a marked increase in vascular tone may affect autoregulatory response.