Brain neuronal nitric oxide synthase neuron-mediated sympathoinhibition is enhanced in hypertensive Dahl rats.
OBJECTIVE
To elucidate the role of central neurons containing neuronal nitric oxide synthase (nNOS neurons) in the sympathetic nervous system in hypertensive Dahl salt-sensitive (DS) rats.


METHODS
Dahl rats were fed either a regular-salt (0.4% NaCl) or high-salt (8% NaCl) diet for 4 weeks. The effect of intracerebroventricular administration of S-methyl-L-thiocitrulline, a selective nNOS inhibitor, on renal sympathetic nerve activity was examined in chronically instrumented conscious DS rats. The activity and protein amount of brain nNOS was evaluated by enzyme assay and western blot analysis. The distribution and number of nNOS neurons in the brainstem were examined immunohistochemically in hypertensive and normotensive DS rats.


RESULTS
S-methyl-L-thiocitrulline induced a larger increase in tonic renal sympathetic nerve activity generated before baroreflex-mediated inhibition in hypertensive DS rats than normotensive DS rats. Hypertensive DS rats showed increased nNOS activity in the brainstem, but not in the diencephalon or cerebellum. High nNOS activity was confirmed by an increase in the amount of nNOS protein. nNOS Neurons were localized in several nuclei throughout the brainstem; the dorsolateral periaqueductal gray, pedunculopontine tegmental nucleus, dorsal raphe nucleus, laterodorsal tegmental nucleus, lateral parabrachial nucleus, rostral ventrolateral medulla, nucleus tractus solitarius and raphe magnus. The number of nNOS neurons in these nuclei, except for the two raphes, was significantly greater in hypertensive than in normotensive DS rats.


CONCLUSIONS
These findings suggest that central nNOS-mediated sympathoinhibition may be enhanced in salt-sensitive hypertensive Dahl rats. The upregulated nNOS-mediated inhibition may occur in the central sympathetic control system generated before baroreflex-mediated inhibition.
Tandai-Hiruma
Megumi
M
Department of Physiology II, National Defense Medical College, Tokorozawa, Saitama, Japan. meguth@cc.ndmc.ac.jp
Horiuchi
Jouji
J
Sakamoto
Hiroshi
H
Kemuriyama
Takehito
T
Hirakawa
Haruhisa
H
Nishida
Yasuhiro
Y
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002956:Citrulline / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology*; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D008526:Medulla Oblongata / Q000166:cytology / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009433:Neural Inhibition / Q000502:physiology*; D009474:Neurons / Q000201:enzymology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D045042:Pedunculopontine Tegmental Nucleus / Q000166:cytology / Q000502:physiology; D010487:Periaqueductal Gray / Q000166:cytology / Q000502:physiology; D011903:Raphe Nuclei / Q000166:cytology / Q000502:physiology; D051381:Rats; D020303:Rats, Inbred Dahl; D017552:Solitary Nucleus / Q000166:cytology / Q000502:physiology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D002956:Citrulline; D001120:Arginine; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D013890:Thiourea; C086717:S-methylthiocitrulline