A role of VentroMedian Medullary Raphe (VMMR) neurons in cardiovascular (CV) control is suggested by studies on anaesthetized animals. VMMR neuron disinhibition increased heart rate, arterial pressure and sympathetic outflow to the heart (1). However, it is thought that VMMR neurons do not maintain the tonic sympathetic CV drive, due to the lack of major CV effects after VMMR inhibition (2). Since general anaesthesia affects sympathetic outflow and does not permit the measurement of heart rate variability (HRV), in the present study the role of VMMR neurons in CV control has been assessed in free behaving rats. Six male CD rats (Charles River), kept under a 12h:12h light-dark cycle at 24±0.5°C ambient temperature were used. Under general anaesthesia (Diazepam, 5mg/Kg intramuscular; Ketamine-HCl, 100 mg/Kg, intraperitoneal), animals were implanted with electrodes for EEG and EKG recording, a thermistor to measure hypothalamic temperature (Thy), a microinjection guide cannula to target VMMR. One week after surgery, rats were randomly microinjected, on different days, with 100nl of the following: i) GABA-A agonist muscimol (1mM); ii) GABA-A antagonist bicuculline (1mM); iii) 0.9% saline. Preliminary analysis of data from muscimol injection was carried out during wake in two rats. HRV was analyzed within both the time (R-R mean; R-R standard deviation (STD-RR); root mean square successive difference (RMSSD)) and frequency domains (High (HF, 0.6–2.4 Hz) and Low Frequency (LF, 0.06–0.6 Hz) bands). Effects of injections were separated into six temporal blocks according to the dynamics of changes in core temperature following VMMR inhibition (3). At the end of the experiment, animals were sacrificed and histological control was carried out. Table 1 shows changes in HRV parameters and Thy (% of baseline levels, mean ± SEM) during the six temporal blocks. The LF band, expression of CV sympathetic drive, was clearly reduced following VMMR neurons inhibition. Changes in HRV parameters appeared to be specifically due to VMMR neuron inhibition and not to changes in Thy. In conclusion, VMMR neurons seem to participate in maintaining tonic sympathetic CV outflow.
M. Cerri, G. Zamboni, D. Tupone, D. Dentico, M. Luppi, D. Martelli, et al. (2009). Role of VentroMedian Medullary Raphe neurons in controlling heart rate variability in free behaving rats.
Role of VentroMedian Medullary Raphe neurons in controlling heart rate variability in free behaving rats
CERRI, MATTEO;ZAMBONI GRUPPIONI, GIOVANNI;TUPONE, DOMENICO;DENTICO, DANIELA;LUPPI, MARCO;MARTELLI, DAVIDE;PEREZ, EMANUELE;AMICI, ROBERTO
2009
Abstract
A role of VentroMedian Medullary Raphe (VMMR) neurons in cardiovascular (CV) control is suggested by studies on anaesthetized animals. VMMR neuron disinhibition increased heart rate, arterial pressure and sympathetic outflow to the heart (1). However, it is thought that VMMR neurons do not maintain the tonic sympathetic CV drive, due to the lack of major CV effects after VMMR inhibition (2). Since general anaesthesia affects sympathetic outflow and does not permit the measurement of heart rate variability (HRV), in the present study the role of VMMR neurons in CV control has been assessed in free behaving rats. Six male CD rats (Charles River), kept under a 12h:12h light-dark cycle at 24±0.5°C ambient temperature were used. Under general anaesthesia (Diazepam, 5mg/Kg intramuscular; Ketamine-HCl, 100 mg/Kg, intraperitoneal), animals were implanted with electrodes for EEG and EKG recording, a thermistor to measure hypothalamic temperature (Thy), a microinjection guide cannula to target VMMR. One week after surgery, rats were randomly microinjected, on different days, with 100nl of the following: i) GABA-A agonist muscimol (1mM); ii) GABA-A antagonist bicuculline (1mM); iii) 0.9% saline. Preliminary analysis of data from muscimol injection was carried out during wake in two rats. HRV was analyzed within both the time (R-R mean; R-R standard deviation (STD-RR); root mean square successive difference (RMSSD)) and frequency domains (High (HF, 0.6–2.4 Hz) and Low Frequency (LF, 0.06–0.6 Hz) bands). Effects of injections were separated into six temporal blocks according to the dynamics of changes in core temperature following VMMR inhibition (3). At the end of the experiment, animals were sacrificed and histological control was carried out. Table 1 shows changes in HRV parameters and Thy (% of baseline levels, mean ± SEM) during the six temporal blocks. The LF band, expression of CV sympathetic drive, was clearly reduced following VMMR neurons inhibition. Changes in HRV parameters appeared to be specifically due to VMMR neuron inhibition and not to changes in Thy. In conclusion, VMMR neurons seem to participate in maintaining tonic sympathetic CV outflow.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
