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(Hypertension. 1999;34:802-807.)
© 1999 American Heart Association, Inc.

Scientific Contributions

Long-Term Nitric Oxide Inhibition and Chronotropic Responses in Rat Isolated Right Atria

Sonia R. Riado; Angelina Zanesco; Louis Allen Barker; Iara M. S. De Luca; Edson Antunes; Gilberto De Nucci

From the Department of Pharmacology, Faculty of Medical Sciences (S.R.A.), the Department of Histology and Embryology, Biology Institute (I.M.S.D.L.), and the Department of Pharmacology, Faculty of Medical Sciences (E.A., G.D.N.), UNICAMP, Campinas, Brazil; the Department of Physical Education, Biosciences Institute, UNESP (A.Z.), Rio Claro, Brazil; and the Department of Pharmacology, Louisiana State University Medical Center (L.A.B.), New Orleans.

Correspondence to Angelina Zanesco, PhD, Department of Physical Education, Bioscience Institute, UNESP, Av 24A n° 1515, Bela Vista, CEP 13506-900, Rio Claro (SP), Brazil. E-mail azanesco{at}bestway.com.br

Abstract—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 ß-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-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 µmol/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 ß-adrenoceptor–mediated and muscarinic receptor–mediated chronotropic responses.

Key Words: adrenergic receptor agonists • receptors, muscarinic • receptors, adrenergic, beta • blood pressure • nitric oxide