Age-related loss of cardiac vagal preganglionic neurones in spontaneously hypertensive rats

Despite the findings that impaired vagal control of the heart rate occurs in human hypertension, leading to greater cardiovascular risk, the mechanism of this impairment is as yet unknown. Observations in humans and experiments in the spontaneously hypertensive rat (SHR) suggested that such impairment may be related to an anomaly in central vagal neurones. We therefore set out to determine whether the numbers and distribution of cardiac-projecting vagal preganglionic neurones in the medulla of adult (12 week) hypertensive SHR are different from those in young (4 week) prehypertensive SHR and in age-matched Wistar-Kyoto (WKY) rats of two age groups. The number of vagal neurones, identified by labelling with the fluorescent tracer DiI applied to the heart, was essentially similar in the three areas of the medulla analysed (dorsal vagal nucleus, nucleus ambiguus and intermediate reticular zone) in young SHR and young or adult WKY rats. In contrast, fewer vagal neurones were labelled in adult SHR compared with young SHR or WKY rats. This difference was due to highly significant reductions in vagal neurones in the dorsal vagal nucleus and nucleus ambiguus on the right side of the medulla. These observations suggest that a loss of parasympathetic preganglionic neurones supplying the heart with axons in the right vagus nerve, or a remodelling of their cardiac projections, may explain the known impairment of the baroreceptor reflex gain controlling heart rate in hypertension.