Role of the spinal cord NO/cGMP pathway in the control of arterial pressure and heart rate.
The modulatory effect of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway on sympathetic preganglionic neurons still deserves further investigation. The present study was designed to examine the role of the spinal cord NO/cGMP pathway in controlling mean arterial pressure and heart rate. We observed that intrathecal administration of the NO synthase inhibitor Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME) causes an increase in mean arterial pressure but does not affect heart rate. Intrathecal administration of the soluble guanylyl cyclase inhibitor 1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) does not change mean arterial pressure and heart rate. The precursor for NO synthesis, L-arginine, reduces both mean arterial pressure and heart rate while administration of ODQ before L-arginine impaired decreases in mean arterial pressure and heart rate. Administration of the N-methyl-D-aspartate (NMDA) receptor antagonist DL-2-amino-5-phosphonopentanoic acid (AP5) after L-NAME does not affect increases in mean arterial pressure promoted by NO synthase inhibition. Although the hypotensive and bradycardic responses induced by intrathecal administration of L-arginine depend on cGMP, our results indicate that NO acts to tonically inhibit SPNs, independent of either cGMP or NMDA receptors.
Department of Physiology, School of Medicine of Ribeirão Preto, University of São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, Brazil.
João Paulo J
JP
Sabino
Gabriela
G
Bombarda
Carlos Alberto A
CA
da Silva
Rubens
R
Fazan
Maria Cristina O
MC
Salgado
Helio C
HC
Salgado
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D006152:Cyclic GMP / Q000502:physiology*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D010069:Oxadiazoles / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology; D013116:Spinal Cord / Q000502:physiology; D013237:Stereoisomerism; D013564:Sympathetic Nervous System / Q000502:physiology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D010069:Oxadiazoles; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D015763:2-Amino-5-phosphonovalerate; D001120:Arginine; D006152:Cyclic GMP; D019331:NG-Nitroarginine Methyl Ester; D004121:Dimethyl Sulfoxide