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P Pagliaro, Letter to the Editor, Cardiovascular Research, Volume 44, Issue 1, October 1999, Page 223, https://doi.org/10.1016/S0008-6363(99)00208-4
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Dear Editor
I read the nicely written and interesting review by Kojda and Kotteberg [1]. I found very interesting the section devoted to the chronotropic effects of NO. I agree with the conclusions of the authors that NO has a positive chronotropic effect which has been described and explained. However, I must note that the in vivo set-up in animals of Krege et al. [2], and of Kojda et al. [3], quoted in this review with the numbers 98 and 99 of the references, are not the most appropriate to claim a negative chronotropic effect for the NO inhibition in vivo. These two papers [2,3] are not appropriate because, as the same authors of the review report, the used inhibitor was NG-l-arginine methyl ester (l-NAME) which could have a muscarinic receptor blocking effect, so that the interpretation of the results becomes difficult. Furthermore, several weeks of oral application of l-NAME usually induces an increase in blood pressure, so that it is not clear whether the observed bradycardia is due to a direct effect of the inhibitor on the sinus node or to a response to the autonomic reflex induced by the increase in pressure. I feel that a paper of ours [4] and the one of Ward and Angus [5] might throw some light on the problem. In our paper [4] we show that, in the anaesthetized dog, NO inhibition with Nϖ-l-Nitro-arginine (lNNA) induces bradycardia even if the vagi are sectioned and any increase in pressure is prevented by connecting the two femoral arteries with a blood reservoir. Our results also indicate that the sympathetic discharge is not affected by the NO-inhibition “per se”, but, before and after NO-inhibition, it can be reduced to the same extent by the same increase in pressure. In their paper Ward and Angus [5], reported that in the rabbit NO-inhibition induces a reduction in heart rate in spite of pharmacological blockade of the autonomic reflexes.
