Role of nitric oxide in regulation of brain stem circulation during hypotension.
We tested the hypothesis that nitric oxide (NO) plays a role in CBF autoregulation in the brain stem during hypotension. In anesthetized rats, local CBF to the brain stem was determined with laser-Doppler flowmetry, and diameters of the basilar artery and its branches were measured through an open cranial window during stepwise hemorrhagic hypotension. During topical application of 10(-5) mol/L and 10(-4) mol/L N(omega)-nitro-L-arginine (L-NNA), a nonselective inhibitor of nitric oxide synthase (NOS), CBF started to decrease at higher steps of mean arterial blood pressure in proportion to the concentration of L-NNA in stepwise hypotension (45 to 60 mm Hg in the 10(-5) mol/L and 60 to 75 mm Hg in the 10(-4) mol/L L-NNA group versus 30 to 45 mm Hg in the control group). Dilator response of the basilar artery to severe hypotension was significantly attenuated by topical application of L-NNA (maximum dilatation at 30 mm Hg: 16 +/- 8% in the 10(-5) mol/L and 12 +/- 5% in the 10(-4) mol/L L-NNA group versus 34 +/- 4% in the control group), but that of the branches was similar between the control and L-NNA groups. Topical application of 10(-5) mol/L 7-nitro indazole, a selective inhibitor of neuronal NOS, did not affect changes in CBF or vessel diameter through the entire pressure range. Thus, endothelial but not neuronal NO seems to take part in the regulation of CBF to the the brain stem during hypotension around the lower limits of CBF autoregulation. The role of NO in mediating dilatation in response to hypotension appears to be greater in large arteries than in small ones.
Toyoda
K
K
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Fujii
K
K
Ibayashi
S
S
Nagao
T
T
Kitazono
T
T
Fujishima
M
M
D000818:Animals; D001488:Basilar Artery / Q000503:physiopathology; D001783:Blood Flow Velocity; D001933:Brain Stem / Q000098:blood supply*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007022:Hypotension / Q000503:physiopathology*; D007191:Indazoles / Q000494:pharmacology; D017078:Laser-Doppler Flowmetry; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects
D004791:Enzyme Inhibitors; D007191:Indazoles; D019335:Nitroarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; C080122:7-nitroindazole