Possible participation of spinal nitric oxide in the control of the blood pressure in anesthetized rats.
In pentobarbital-anesthetized rats the intrathecal (i.t.) injection of the nitric oxide (NO) precursor, L-arginine (10 and 20 micromol), elicited a decrease in the mean blood pressure (MBP) whereas the inhibitor of the NO synthase (NOS) N(G)-nitro-L-arginine methyl ester (L-NAME; 0.1-10 micromol) produced a dose-dependent pressor effect. The pressor response to L-NAME was prevented by pretreatment with L-arginine. Neither D-arginine nor D-NAME modified the MBP. The NO donor sodium nitroprusside (SNP; 0.125 and 0.25 micromol, i.t.) induced a hypotensive response followed by a pressor effect. The dual response to SNP as well as the hypotensive effect of L-arginine were abolished by the guanylate cyclase inhibitor Methylene blue (0.3 micromol, i.t.). Nicotinic ganglionic blockade by hexamethonium (10 mg/kg, i.v.) reduced the hypotensive effects of both L-arginine and SNP and prevented almost completely the pressor effects of either L-NAME or SNP. The pressor effect of L-NAME was abolished by 2-amino-5-phosphonovaleric acid (APV; 30 nmol, i.t.), a selective antagonist of glutamate receptors of the NMDA subtype. These results suggest that in the spinal cord of pentobarbital-anesthetized rats NO exerts both inhibitory and excitatory effects on the preganglionic sympathetic nerve activity related to the control of the BP. The synthesis of NO appears to be tonically activated through the stimulation of spinal glutamate receptors of the NMDA subtype.
del Carmen García
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Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Celuch
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SM
Adler-Graschinsky
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D000768:Anesthesia, General; D000818:Animals; D001339:Autonomic Fibers, Preganglionic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005730:Ganglionic Blockers / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D007278:Injections, Spinal; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D010424:Pentobarbital; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects
D004791:Enzyme Inhibitors; D005730:Ganglionic Blockers; D009599:Nitroprusside; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D010424:Pentobarbital; D019331:NG-Nitroarginine Methyl Ester