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

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 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.

Cardiac Mitochondrial Nitric Oxide: A Regulator of Heart Rate?

“…Because other authors have shown that the NO system is related to a bradycardic effect (experiments in NOS knockout mice, applications of NO donors and/or NOS inhibitors), 11,22 , our findings can be interpreted, in this context, as suggesting a direct negative chronotropic effect of NO on the pacemaker activity. Our results support the idea that the L-NAME-induced tachycardia observed in in vivo experiments is not caused by direct action of the inhibitor on the showed that L-NAME did not affect the beat rate, 23 whereas others have reported that low doses of an NO donor or 8-bromo-cGMP increase the spontaneous beating rate in atria isolated from guinea-pig and in sinoatrial node cells from rabbit, by activation of the hyperpolarization inward current. 24 Taking our results into consideration, it is probable that other humoral factors may be involved in the L-NAME-induced tachycardia in autonomic-blocked rats.…”

Long‐term nitric oxide deficiency causes muscarinic supersensitivity and reduces β3‐adrenoceptor‐mediated relaxation, causing rat detrusor overactivity

“…Age‐matched control rats received tap water alone. Systolic blood pressure was measured by using a modified tail‐cuff method in conscious animals ( Riado et al , 1999 ).…”

Effect of acute nitric oxide synthase inhibition in the modulation of heart rate in rats

“…The L-NAME-induced tachycardia observed in in vivo experiments may not be due to a direct action of the inhibitor on the pacemaker. In isolated right atria, Riado et al (27) showed that L-NAME did not affect the beat rate, whereas others have reported that low doses of an NO donor or 8-bromo-cGMP increase the spontaneous beating of isolated guinea pig atria and rabbit sinoatrial node cells by activation of the hyperpolarization inward current (28,29). In addition, NO can elicit either positive or negative inotropic effects (30,31).…”