Control of cardiac rate, contractility, and atrioventricular conduction by medullary raphé 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.

Asymmetry in the control of cardiac performance by dorsomedial hypothalamus

“…It must be acknowledged that LVEDP is an indirect estimate of the left ventricular volume and could be used as an index of preload only if the ventricular compliance remains constant. Finally, as LVdP/dt in the rat heart is strongly affected by afterload (24, 42), we have controlled for this confounder by comparing ⌬(LVdP/dt)/ ⌬MAP ratio for DMH-induced responses to that provoked by administration of ␣-adrenergic agonist phenylephrine (30). As expected, phenylephrine provoked both pressor and contractile effect, but the magnitude of this afterload-induced contractile response was substantially smaller than the DMH-induced inotropic effect.…”

“…In discussing this possibility, we would like to consider two medullary regions: the rostral ventrolateral medulla (RVLM) and the medullary raphe/parapyramidal area. In rats, chemical activation of either of these areas causes sympathetically mediated tachycardia and rise in cardiac contractility (3,4,6,30). Furthermore, anatomical tracing studies have demonstrated that both regions receive direct projections from the DMH (14,37) and that both regions, in turn, project to the heart, including to the ventricular myocardium (36,38,48).…”

“…Whether presympathetic pathways for the control of cardiac inotropic function are arranged in a similar way remains an open question. Lack of changes in cardiac sympathetic activity, HR, or contractile responses to microinjection of GABA into the raphe area indicates that raphe-spinal cardiomotor neurons are not tonically active (5,30), at least in anesthetized animals. For elaborated discussion of functional specialization of neurons controlling cardiac function (see Ref.…”

Oestrogen receptors in the central nervous system and evidence for their role in the control of cardiovascular function

“…The midline raphé nuclei of the medulla oblongata, comprising predominantly 5-HT producing neurones, contain rather ill-defined sites shown to regulate cardiovascular function, as well as respiratory, thermoregulatory and (anti-) nociceptive functions (Blessing, 1997). Neurones in this region, including those of the parapyramidal area and rostroventromedial medulla have projections to the spinal IML and may function as sympathetic premotor neurones (Blessing, 1997;Salo et al, 2009;Goodchild and Moon, 2009). The midbrain dorsal raphé nuclei of primates and rodents strongly express ERb receptors, which have been shown to mediate changes in gene expression in 5-HT neurones, providing a substrate for oestrogen's effects on mood, arousal, pain perception and other neural functions (Bethea et al, 2002).…”

Brainstem control of cerebral blood flow and application to acute vasospasm following experimental subarachnoid hemorrhage

“…This region has long been known to modulate sensorimotor processing important for nocifensor behaviors (Heinricher and Ingram, 2008), and has also been implicated in regulation of some sympathetic outflows, based on both anatomical and functional studies (Ter Horst et al, 1996; Blessing, 1997; Horiuchi et al, 2004; Nakamura et al, 2004; Kerman, 2008; Morrison et al, 2008; Salo et al, 2009). Positive and negative modulation of nociception and various aspects of autonomic regulation appear to be mediated by distinct RVM cell populations, but are likely recruited in a coordinated manner to orchestrate behavioral and physiological responses to internal and external threats (Lovick, 1997; Heinricher et al, 2009; Martenson et al, 2009).…”