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Stimulation of Locus Coeruleus Inhibits the Cardiogenic Sympathetic Afferent Reflex in Rats
Author(s) -
Yobst Nathan,
Dubey Rashmi,
Zahner Matthew
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2021.35.s1.03637
Subject(s) - rostral ventrolateral medulla , locus coeruleus , medicine , reflex , heart rate , microinjection , stimulation , blood pressure , endocrinology , hypothalamus , baroreceptor , anesthesia , central nervous system
Ischemic stimulation of cardiac sensory afferents causes chest pain and an increase in sympathetic vasomotor activity. This sympathetic reflex, which increases blood pressure and heart rate, is referred to as the cardiogenic sympathetic afferent reflex (CSAR). While the CSAR may be important for the maintenance of blood perfusion of vital organs, the increased sympathetic activity may also be detrimental because it further increases the oxygen demand of the ischemic myocardium. While the brain stem nuclei, such as the nucleus tractus solitarius and rostral ventrolateral medulla have been shown to play an important role in the CSAR, the role of other brain stem nuclei and the sources that regulate sympathetic activity in the CSAR are still not clear. We have previously characterized the role of hypothalamic nuclei in the CSAR and have shown that acute chemical inhibition of the paraventricular nucleus but not the dorsomedial hypothalamus attenuates the CSAR. However, little is known regarding other brain stem sites involved in the regulation of sympathetic activity. In this study, we tested the hypothesis that “stimulation of the locus coeruleus (LC) attenuates the CSAR in rats”. Renal sympathetic nerve activity (RSNA), blood pressure, and heart rate were recorded in anesthetized and cervically vagotomized rats during epicardial application of bradykinin (BK 10 μg/ml). Unilateral microinjection of glutamate (2.5 nmol in 50 nl), was used to stimulate the LC. Vehicle injection into the LC had no significant effect (n=10, P > 0.05) on blood pressure, heart rate, or RSNA. In vehicle‐injected rats, epicardial BK application significantly increased (P < 0.05) RSNA to 253.5 ± 19.0% of baseline, heart rate from 335.7 ± 14.0 to 351.4 ± 10.5 bpm, and blood pressure from 103.4 ± 3.5 mmHg to 131.4 ± 4.1 mmHg. In a separate group of rats (n=10) glutamate microinjection into the LC significantly (P < 0.05) reduced basal RSNA to 40.2 ± 7.0% of baseline and blood pressure to 60.4 ± 5.0 mmHg, but did not significantly decrease heart rate (329.3 ± 12.5 bpm, P > 0.05). In this group of rats, although epicardial BK application significantly increased (P < 0.05) RSNA to 118.3 ± 19.3% of baseline and blood pressure to 129.5 ± 6.6 mmHg the reflex response to epicardial BK application on RSNA, blood pressure, and heart rate, was significantly attenuated (P < 0.05) compared with the respective controls. These results suggest that the brain stem pathways involving LC inputs to sympathetic vasomotor pathways are important for the regulation of the CSAR.