Nitric oxide modulates the cardiovascular effects elicited by acetylcholine in the NTS of awake rats.
Microinjection of acetylcholine chloride (ACh) in the nucleus of the solitary tract (NTS) of awake rats caused a transient and dose-dependent hypotension and bradycardia. Because it is known that cardiovascular reflexes are affected by nitric oxide (NO) produced in the NTS, we investigated whether these ACh-induced responses depend on NO in the NTS. Responses to ACh (500 pmol in 100 nl) were strongly reduced by ipsilateral microinjection of the NOS inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 nmol in 100 nl) in the NTS: mean arterial pressure (MAP) fell by 50 +/- 5 mmHg before L-NAME to 9 +/- 4 mmHg, 10 min after L-NAME, and HR fell by 100 +/- 26 bpm before L-NAME to 20 +/- 10 bpm, 10 min after L-NAME (both P < 0.05). Microinjection of the selective inhibitor of neuronal nitric oxide synthase (nNOS), 1-(2-trifluoromethylphenyl) imidazole (TRIM; 13.3 nmol in 100 nl), in the NTS also reduced responses to ACh: MAP fell from 42 +/- 3 mmHg before TRIM to 27 +/- 6 mmHg, 10 min after TRIM (P < 0.05). TRIM also tended to reduce ACh-induced bradycardia, but this effect was not statistically significant. ACh-induced hypotension and bradycardia returned to control levels 30-45 min after NOS inhibition. Control injections with D-NAME and saline did not affect resting values or the response to ACh. In conclusion, injection of ACh into the NTS of conscious rats induces hypotension and bradycardia, and these effects may be mediated at least partly by NO produced in NTS neurons.
da Silva
Liana Gouveia
LG
Department of Physiology, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Botucatu 862, São Paulo, SP 04023-60, Brazil.
Dias
Ana Carolina Rodrigues
AC
Furlan
Elaina
E
Colombari
Eduardo
E
D000109:Acetylcholine / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001919:Bradycardia / Q000378:metabolism / Q000503:physiopathology; D002319:Cardiovascular System / Q000294:innervation*; D002799:Cholinergic Fibers / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007022:Hypotension / Q000378:metabolism / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D026602:Nitrergic Neurons / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D017208:Rats, Wistar; D017552:Solitary Nucleus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors; D014851:Wakefulness
D004791:Enzyme Inhibitors; D007093:Imidazoles; C098186:1-(2-trifluoromethylphenyl)imidazole; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester