Heart rate (HR) dynamics were investigated in mice deficient in monoamine oxidase A and B, whose phenotype includes elevated tissue levels of norepinephrine, serotonin, dopamine, and phenylethylamine. In their home cages, spectral analysis of R-R intervals revealed more pronounced fluctuations at all frequencies in the mutants compared with wild-type controls, with a particular enhancement at 1-4 Hz. No significant genotypic differences in HR variability (HRV) or entropies calculated from Poincaré plots of the R-R intervals were noted. During exposure to the stress of a novel environment, HR increased and HRV decreased in both genotypes. However, mutants, unlike controls, demonstrated a rapid return to baseline HR during the 10-min exposure. Such modulation may result from an enhanced vagal tone, as suggested by the observation that mutants responded to cholinergic blockade with a decrease in HRV and a prolonged tachycardia greater than controls. Monoamine oxidase-deficient mice may represent a useful experimental model for studying compensatory mechanisms responsible for changes in HR dynamics in chronic states of high sympathetic tone.
Keywordsserotonin; norepinephrine; cholinergic; arrhythmia; heart rate variability; vagus nerve; sympathetic; parasympathetic ENZYMATIC DEGRADATION by monoamine oxidase (MAO)-A and -B plays a crucial role in the regulation of tissue levels of serotonin (5-HT), norepinephrine (NE), epinephrine, Address for reprint requests and other correspondence: D. P. Holschneider, Dept. of Psychiatry, Univ. of Southern California, Keck School of Medicine, LAC-USC Hosp., 1200 N. State St., Rm. 10-621, Los Angeles, CA 90089 (holschne@hsc.usc.edu)..
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Author ManuscriptAm J Physiol Heart Circ Physiol. Author manuscript; available in PMC 2014 June 30.
NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript phenylethylamine, and dopamine. Our laboratory has recently identified (29) a natural mutation of MAO-A occurring in mice with targeted deletion of the . These mice doubly deficient in both MAO isoforms [MAO-A/B knockout (KO)] demonstrate brain levels of 5-HT, NE, dopamine, and phenylethylamine that are increased 8.5-, 2.2-, 1.7-, and 15.7-fold above those noted in adult, wild-type (WT) animals, with levels of the 5-HT metabolite 5-hydroxyindoleacetic acid essentially undetectable in both the brain and urine.When these neuroactive compounds are administered acutely, they show cardiac electrophysiological effects, including changes in the dynamics of the sinoatrial node and in the atrioventricular conduction, as well as in the ventricular fibrillation threshold (11,18,27,31,36). On the other hand, the results of chronic catecholamine elevations observed in patients are more mixed, showing both paroxysmal tachycardia as well as occasional bradyarrhythmias (3,28,39). The elevated bioamine levels observed in the MAO-A/B KO mice since early development could certainly alter their cardiovascular autonomic control; however, it is not immediately apparent how t...
