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NEUROHUMORAL CONTROL OF CARDIOVASCULAR FUNCTION

Dorsomedial hypothalamic sites where disinhibition evokes tachycardia correlate with location of raphe-projecting neurons

²Department of Pharmacology and Toxicology and ¹Program in Medical Neurobiology, Indiana University School of Medicine, Indianapolis, Indiana 46202

Submitted 18 November 2003 ; accepted in final form 2 April 2004

Disinhibition of neurons in the region of the dorsomedial hypothalamus (DMH) elicits sympathetically mediated tachycardia in rats through activation of the brain stem raphe pallidus (RP), and this same mechanism appears to be largely responsible for the increases in heart rate (HR) seen in air jet stress in this species. Neurons projecting to the RP from the DMH are said to be concentrated in a specific subregion, the dorsal hypothalamic area (DA). Here, we examined the hypothesis that the location of RP-projecting neurons in the DA correspond to the sites at which microinjection of bicuculline methiodide (BMI) evokes the greatest increases in HR. To determine the distribution of RP-projecting neurons in the DA, cholera toxin B was injected in the RP in four rats. A consistent pattern of retrograde labeling was seen in every rat. In the hypothalamus, RP-projecting neurons were most heavily concentrated midway between the mammillothalamic tract and the dorsal tip of the third ventricle dorsal to the dorsomedial hypothalamic nucleus 3.30 mm caudal to bregma. In a second series of experiments, the HR response to microinjections of BMI (2 pmol/5 nl; n = 76) was mapped at sites in the DA and surrounding areas in 22 urethane-anesthetized rats. All injection sites were located from 2.56 to 4.16 mm posterior to bregma, and the microinjections that evoked the largest increase in HR (i.e., >100 beats/min in some instances) were located in a region where RP-projecting neurons were most densely concentrated. Thus RP-projecting neurons in the DA may mediate DMH-induced tachycardia and thus play a role in stress-induced cardiac stimulation.

dorsomedial hypothalamus; sympathetic nervous system; dorsal hypothalamic area

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