Blockade of spinal nitric oxide synthase on blood pressure variability and hepatic microcirculation.
BACKGROUND
We previously demonstrated that intrathecal administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, increased systemic arterial blood pressure in a dose-dependent manner in rats. The aim of the study was to investigate the participation of autonomic nervous system on L-NAME-induced hypertension and also illuminate its effects on hepatic microcirculation in rats.


METHODS
Eight Spraque-Dawley rats were used and initially anesthetized with ketamine 120 mg/kg, intraperitoneally supplemented by intravenous infusion of ketamine at 30 mg/kg/h for maintenance. Surgical preparations included cannulations of right femoral artery and vein to obtain systemic arterial pressure signals and administer anesthetic drug. A mini-laparotomy was made to facilitate the insertion of a microdialysis probe and attachment of a laser Doppler probe to the middle lobe of the liver. On experiment, L-NAME was administered via the previously placed intrathecal catheter at 0, 0.37, 0.74, and 1.48 micromol in sequence at a 2-h interval.


RESULTS
The results showed that the arterial blood pressure increased in a dose-dependent manner. By the same token, the power density of very low frequency (VLF) also increased. The low frequency (LF): high frequency (HF) ratio shifted toward parasympathetic dominance. Blood flow to the liver was unchanged except slightly decreased in the animals receiving 0.37 micromol. The levels of monoethylglycinexylidide (MEGX), an index of hepatic metabolism, were unchanged throughout the experiment.


CONCLUSIONS
We concluded that the blockade of spinal nitric oxide synthase by intrathecal administration of L-NAME significantly increased vasomotor tone in a dose-dependent manner and as a consequence induced a reflex sympathetic inhibition. Hepatic microcirculation was stable with the applied doses.
Chen
Chih-Hung
CH
Department of Anesthesiology, Hualien Army General Hospital, Hualien, Taiwan.
Shyr
Ming-Hwang
MH
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007278:Injections, Spinal; D008099:Liver / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects* / Q000201:enzymology
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester