POSSIBLE ROLE OF NITRIC-OXIDE IN AUTOREGULATORY RESPONSE IN RAT INTRACEREBRAL ARTERIOLES

OBJECTIVE: Cerebral autoregulation is an important regulatory mechanis m that maintains a constant cerebral blood flow over a wide range of p erfusion pressures. The goal of this study was to determine whether ni tric oxide contributes to the autoregulatory response of cerebral arte rioles to altered transmural pressure (TMP). METHODS: Seventy-nine int raparenchymal arterioles (53.6 +/- 3.5 mu m mean diameter) isolated fr om rats were cannulated with micropipettes and pressurized at a TMP of 60 mm Hg (control pressure). Vessel diameters were monitored continuo usly using a video dimensional analyzer. The autoregulatory diameter r esponses to varying intraluminal pressures were observed in the presen ce and absence of a nitric oxide synthase inhibitor, N-G-monomethyl-L- arginine (L-NMMA). The effect of L-NMMA-induced constriction on autore gulatory response also was compared with responses after prostaglandin F-2 alpha and alkalosis-induced constrictions. RESULTS: Autoregulator y responses were observed over a range from 10 to 90 mm Hg of TMP. Tre atment with 10(-4) mol/L L-NMMA constricted arterioles and inhibited t he autoregulatory vasodilation to TMP reductions from 60 mm Hg to 10 o r 30 mm Hg. In L-NMMA-treated arterioles, elevation in TMP from 60 to 90 mm Hg caused an autoregulatory vasoconstriction. Treatment with alk aline pH 7.65 constricted arterioles to a similar degree as that induc ed by L-NMMA at 60 mm Hg, and under these conditions, the autoregulato ry response remained intact. Arterioles severely constricted with pros taglandin F-2 alpha showed no significant autoregulatory response. CON CLUSION: These results suggest that 1) vascular nitric oxide release i ncreases in response to a decrease in TMP from 60 mm Hg, thereby contr ibuting to the autoregulatory vasodilation intrinsic to the vessel dur ing 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 a utoregulatory response.