NITRIC-OXIDE REGULATES CEREBRAL ARTERIOLAR TONE IN RATS

Background and Purpose Although cerebral penetrating arterioles are ma in regulators of the brain microcirculation, little is known about the effect of endothelium-derived relaxation factor on these vessels. Thi s study examined the effects of nitric oxide synthase inhibitors on th e spontaneous tone of isolated rat cerebral arterioles. Methods Intrap arenchymal penetrating arterioles (53 to 102 mu m in passive diameter) isolated from Sprague-Dawley rats were cannulated with glass pipettes and subjected to 60 mmHg of intraluminal pressure. The diameter respo nse to intraluminal and extraluminal treatments was observed with an i nverted microscope. Results Extraluminal application of N-w-nitro-L-ar ginine (10(-5) mol/L) contracted the arterioles to 63.9+/-2.8% (P<.05) of the control diameter. This contracting effect was stereospe- cific and easily reversed by L-arginine dose dependently (10(-3), 10(-2) mo l/L) but not by D-arginine. Intraluminally applied N-w-nitro-L-arginin e also induced a similar degree of contraction. Another nitric oxide s ynthase inhibitor, NG-monomethyl L-arginine (10(-5), 10(-4) mol/L), ap plied extraluminally induced a dose-dependent contraction to 77.5+/-6. 6% and 68.6+/-5.4% of the control (P<.05), which was also reversed by L-arginine. L-Arginine alone did not significantly affect vessel diame ter, however. Treatment with indomethacin, a cyclooxygenase inhibitor, dilated the vessel to 115.2+/-7% (P<.05) but did not change the const ricting effect of N-w-nitro-L-arginine. Conclusions N-w-Nitro-L-argini ne and N-G-monomethyl L-arginine produce substantial contraction in is olated brain arterioles, suggesting that nitric oxide of brain arterio les is continuously produced within the vessel wall. The dilatory effe ct of indomethacin appears to be independent of the vasoconstriction i nduced by nitric oxide synthase inhibitor. In these vessels, the effec t of nitric oxide synthase inhibitors is not mediated by an indomethac in-sensitive mechanism. A balance probably exists between factors tend ing to constrict these arterioles and the elaboration of nitric oxide from endothelial cells, which tends to dilate them. The production of nitric oxide from isolated vessels indicates that parenchymal and vess el wall sources of nitric oxide are probably important in brain microc irculatory regulation.