Control of cardiac rate, contractility, and atrioventricular conduction by medullary raphe neurons in anesthetized rats

Abstract

The sympathetic actions of medullary raphé neurons on heart rate (HR), atrioventricular conduction, ventricular contractility, and rate of relaxation were examined in nine urethane-anesthetized (1-1.5 g/kg iv), artificially ventilated rats that had been adrenalectomized and given atropine methylnitrate (1 mg/kg iv). Mean arterial pressure (MAP), ECG, and left ventricular pressure were recorded. The peak rates of rise and fall in the first derivative of left ventricular (LV) pressure (dP/dtmax and dP/dtmin, respectively) and the stimulus-R ($-R) interval were measured during brief periods of atrial pacing at 8.5 Hz before and after ventral medullary raphé neurons were activated by dl-homocysteic acid (DLH, 0.1 M) or inhibited by GABA (0.3 M) in local microinjections (90 nl). LV dP/dtmax values were corrected for the confounding effect of MAP, determined at the end of the experiments after giving propranolol (1 mg/kg iv) to block sympathetic actions on the heart. DLH microinjections into the ventral medullary raphé region increased HR by 44 +/- 2 beats/min, LV dP/dtmax by 1,055 +/- 156 mmHg/s, and the negative value of LV dP/dtmin by 729 +/- 204 mmHg/s (all, P < 0.001) while shortening the $-R interval by 2.8 +/- 0.8 ms (P < 0.01). GABA microinjections caused no significant change in HR, LV dP/dtmax, or $-R interval but reduced LV dP/dtmin from -5,974 +/- 93 to -5,548 +/- 171 mmHg/s and MAP from 115 +/- 4 to 105 +/- 5 mmHg (both, P < 0.01). Rises in tail skin temperature confirmed that GABA injections effectively inhibited raphé neurons. When activated, the neurons in the ventral medullary raphé region thus enhance atrioventricular conduction, ventricular contractility, and relaxation in parallel with HR, but they provide little or no tonic sympathetic drive to the heart.

Fig. 1.

Representative chart records from a single rat showing heart rate [HR, in beats/min (bpm)], mean arterial pressure (MAP, in mmHg), the first derivative of left ventricular (LV) pressure (LV dP/dt, in mmHg/s), and tail skin temperature (Temp, in °C). A and B: responses to microinjection into the medullary raphé of dl-homocysteic acid (DLH) and GABA, respectively. C: responses to intravenous propranolol. Injection times are marked with arrows. Note that near the beginning and end of each trace the heart was paced at 8.5 Hz for ∼10 s.

Fig. 2.

Grouped data showing the change from pretest baseline of HR (in beats/min; A), peak value of LV dP/dt (dP/dt_max, in mmHg/s; B), stimulus-R interval ($-R interval, in ms; C), minimum value of LV dP/dt (LV dP/dt_min, in mmHg/s; D), and tail skin temperature (in °C; E). Responses to raphé microinjections of DLH are shown by white bars, responses to raphé GABA injections by dotted bars, and responses to intravenous propranolol by striped bars. *Significant changes. F: effect of MAP (in mmHg) on LV dP/dt_max (in mmHg/s) in 4 rats showing individual regression lines (details in text).

Fig. 3.

Coronal sections of rostral medulla, redrawn from levels bregma −11.3 mm and bregma −11.6 mm in the atlas of Paxinos and Watson (36). The centers of the DLH and GABA injection sites in 9 rats are shown by the gray-filled circles. P, pyramidal tract; RPa, raphé pallidus nucleus; VII, facial nucleus.