Nitric oxide regulates cerebral arteriolar tone in rats.
OBJECTIVE
Although cerebral penetrating arterioles are main regulators of the brain microcirculation, little is known about the effect of endothelium-derived relaxation factor on these vessels. This study examined the effects of nitric oxide synthase inhibitors on the spontaneous tone of isolated rat cerebral arterioles.


METHODS
Intraparenchymal penetrating arterioles (53 to 102 microns in passive diameter) isolated from Sprague-Dawley rats were cannulated with glass pipettes and subjected to 60 mm Hg of intraluminal pressure. The diameter response to intraluminal and extraluminal treatments was observed with an inverted microscope.


RESULTS
Extraluminal application of Nw-nitro-L-arginine (10(-5) mol/L) contracted the arterioles to 63.9 +/- 2.8% (P < .05) of the control diameter. This contracting effect was stereospecific and easily reversed by L-arginine dose dependently (10(-3), 10(-2) mol/L) but not by D-arginine. Intraluminally applied Nw-nitro-L-arginine also induced a similar degree of contraction. Another nitric oxide synthase inhibitor, NG-monomethyl L-arginine (10(-5), 10(-4) mol/L), applied 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 diameter, however. Treatment with indomethacin, a cyclooxygenase inhibitor, dilated the vessel to 115.2 +/- 7% (P < .05) but did not change the constricting effect of Nw-nitro-L-arginine.


CONCLUSIONS
Nw-Nitro-L-arginine and NG-monomethyl L-arginine produce substantial contraction in isolated brain arterioles, suggesting that nitric oxide of brain arterioles is continuously produced within the vessel wall. The dilatory effect of indomethacin appears to be independent of the vasoconstriction induced by nitric oxide synthase inhibitor. In these vessels, the effect of nitric oxide synthase inhibitors is not mediated by an indomethacin-sensitive mechanism. A balance probably exists between factors tending 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 vessel wall sources of nitric oxide are probably important in brain microcirculatory regulation.
Department of Neurological Surgery, Washington University, School of Medicine, St Louis, Mo.
M
M
Kimura
H H
HH
Dietrich
R G
RG
Dacey
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000187:drug effects / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D019335:Nitroarginine; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D014666:Vasomotor System / Q000187:drug effects*; D019323:omega-N-Methylarginine
D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D007213:Indomethacin