Diminished baroreflex control of heart rate responses in otoconia-deficient C57BL/6JEi head tilt mice

Abstract

The maintenance of stable blood pressure during postural changes is known to involve integration of vestibular and cardiovascular central regulatory mechanisms. Sensory activity in the vestibular system plays an important role in cardiovascular regulation. The purpose of this study was to determine the role of vestibular gravity receptors in normal baroreflex function. Baroreflex heart rate (HR) responses to changes in blood pressure (BP) in otoconia-deficient head tilt (het) mice (n = 8) were compared with their wild-type littermates (n = 12). The study was carried out in conscious male mice chronically implanted with arterial and venous catheters for recording BP and HR and for the infusion of vasoactive drugs. Resting HR was higher in the het mice (661 +/- 13 beats/min) than in the wild-type mice (579 +/- 20 beats/min). BP was comparable in the het (113 +/- 4 mmHg) and wild-type mice (104 +/- 4 mmHg). The slopes of reflex decreases in HR in response to phenylephrine (PE) were blunted in the het mice (-5.5 +/- 1.5 beats x min(-1) x mmHg(-1)) compared with the wild-type mice (-8.5 +/- 0.9 beats x min(-1) x mmHg(-1)). Likewise, reflex tachycardic responses to decreases in BP with sodium nitroprusside (SNP) were significantly blunted in the het mice (-0.8 +/- 0.3 beats x min(-1) x mmHg(-1)) versus the wild-type mice (-2.2 +/- 0.6 beats x min(-1) x mmHg(-1)). Frequency-domain analysis of the HR variability suggests that under resting conditions, parasympathetic contribution was lower in the het versus wild-type mice. Mapping of the expression of immediate-early gene product, c-Fos, in forebrain and brain stem nuclei in response to a BP challenge showed no differences between the wild-type and het mice. These results suggest that tonic activity of gravity receptors modulates and is required for normal function of the cardiac baroreflexes.

Resting Discharge Patterns of Macular Primary Afferents in Otoconia-Deficient Mice

“…The range of normalized CV* values obtained from mice of the present study is comparable to that reported for mouse canal afferents (Lasker et al 2008;Yang and Hullar 2007). The range of CVs as well as the mean CV for the OTO+ data closely approximate those reported in Figure 1 of Yang and Hullar (2007) for "wild-type" C57 mice (no significant difference, p90.2).…”

“…The range of CVs as well as the mean CV for the OTO+ data closely approximate those reported in Figure 1 of Yang and Hullar (2007) for "wild-type" C57 mice (no significant difference, p90.2). Moreover, there is no significant difference in the distribution of CV-ISI pairs obtained from normal mice of the two studies (i.e., OTO+ mice in the present study and C57 wild-type mice; Yang and Hullar 2007; chi-square, p=0.1).…”

“…Cells contributing to the resting discharge data were obtained from 86 mice (49 normal and 37 otoconiadeficient). The probability of isolating cells for study was essentially the same for each genotype and similar to other studies of mouse vestibular primary afferent neurons (Yang and Hullar 2007). On average, approximately three neurons were obtained from each animal regardless of phenotype [ratio of neurons to animals: het+/−, 91/27; het−/−, 57/16; tlt−/−, 56/21; tlt+/−, 52/22].…”

“…These authors have argued that because CV for a given neuron can take on wide ranging values and because the curves of individual neurons tend not to intersect those of other neurons, cells may be uniquely ranked based on CV provided the comparison across neurons is made at the same discharge rate. For these reasons, procedures for normalizing CV for particular rates (generally designated CV*) have been developed and widely used e.g., Baird and Lewis 1986;Goldberg et al 1982Goldberg et al , 1990bLasker et al 2008;Yang and Hullar 2007). Here, we normalized CV to a 15-ms interval based on the coefficients of Baird et al (1988) for the chinchilla and on those of Lasker et al (2008)for the mouse.…”

“…It is well known that this tonic discharge activity has a powerful influence on motor control systems in the brainstem (Goldberg 2000;e.g., Precht et al 1966). Less well appreciated is the fact that tonic gravity receptor discharge may strongly influence regulatory systems located in the brainstem and at more rostral levels of the neuraxis in mature animals (e.g., Fuller et al , 2004Xue et al 2004;Yates and Miller 1998). The findings of elevated discharge rates in OTO− mice may have a bearing on altered baroreflexes reported for these animals [in het(−/−) mice, Xue et al 2004] and may help explain the tonic vestibular influence inferred by these authors as well as the slightly elevated baseline heart rates reported.…”