Long-term nitric oxide inhibition and chronotropic responses in rat isolated right atria.
The long-term administration of nitric oxide synthesis inhibitors induces arterial hypertension accompanied by left ventricular hypertrophy and myocardial ischemic lesions. Because the enhancement of sympathetic drive has been implicated in these phenomena, the current study was performed to determine the potency of beta-adrenoceptor agonists and muscarinic agonists on the spontaneous rate of isolated right atria from rats given long-term treatment with the nitric oxide inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). Atrial lesions induced by long-term treatment with L-NAME were also evaluated. Long-term L-NAME treatment caused a time-dependent, significant (P<0.05) increase in tail-cuff pressure compared with control animals. Our results showed that the potency of isoproterenol, norepinephrine, carbachol, and pilocarpine in isolated right atria from rats given long-term treatment with L-NAME for 7, 15, 30, and 60 days was not affected as compared with control animals. Addition of L-NAME in vitro (100 microl/L) affected neither basal rate nor chronotropic response for isoproterenol and norepinephrine in rat heart. Stereological analysis of the right atria at 15 and 30 days revealed a significant increase on amount of fibrous tissues in L-NAME-treated groups (27+/-2.3% and 28+/-1.3% for 15 and 30 days, respectively; P<0.05) as compared with the control group (22+/-1.1%). Our results indicate that nitric oxide does not to interfere with beta-adrenoceptor-mediated and muscarinic receptor-mediated chronotropic responses.
Riado
S R
SR
Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, Campinas, Brazil.
Zanesco
A
A
Barker
L A
LA
De Luca
I M
IM
Antunes
E
E
De Nucci
G
G
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006325:Heart Atria / Q000503:physiopathology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013564:Sympathetic Nervous System / Q000503:physiopathology*; D016278:Ventricular Function, Right / Q000187:drug effects
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester