Blood pressure control by caudal ventrolateral medulla

  • Schreihofer, Ann (PI)

Project Details


[unreadable] DESCRIPTION (provided by applicant): The brain plays an important role in the regulation of arterial pressure (AP) via the autonomic nervous system. The long range goal of the applicant is to understand how the central nervous system (CNS) controls sympathetic vasomotor tone under conditions of normal AP and how the function is altered with hypertension. Many forms of hypertension are linked with elevated sympathetic nerve activity (SNA), although the basis of this sympatho-activation is not well understood. Normally, SNA is restrained by GABAergic neurons in the caudal ventrolateral medulla (CVLM) to maintain a consistent AP. For the short-term control of SNA and AP, these GABAergic CVLM neurons are an essential link in the central pathway for the baroreceptor reflex. However, GABAergic CVLM neurons also are clearly important for setting the long-term level of SNA independent of the baroreflex. We have observed that in the chronic absence of baroreceptor inputs or their site of termination in the nucleus tractus solitarius (NTS), the restoration of a normal mean AP is associated with a normal CVLM-mediated inhibition of SNA and AP. In contrast, spontaneously hypertensive rats have elevated SNA which may be linked with impaired CVLM-mediated inhibition of SNA and AP. Apart from baroreceptor inputs and the NTS, little is known about the central mechanisms regulating the activity of these powerful GABAergic CVLM neurons. This project will use a combination of state-of-the-art methods in rats (i.e. electrophysiological, neuroanatomical, and molecular approaches) to determine how other areas of the brain regulate the activity of GABAergic CVLM neurons under normotensive and hypertensive conditions. Specifically, we will determine whether identified glutamatergic inputs to the CVLM from the paraventricular nucleus of the hypothalamus and ventrolateral periaqueductal gray activate GABAergic CVLM neurons that project to the rostral ventrolateral medulla (RVLM). We will use chronic arterial baroreceptor denervated rats as a normotensive model to examine inputs to GABAergic CVLM neurons that may be masked by powerful baroreceptor inputs. In addition, we will determine whether the CVLM-mediated inhibition of SNA is impaired in spontaneously hypertensive rats. Collectively, these studies will provide a sophisticated analysis of the mechanisms underlying the brainstem's role in the long-term regulation of sympathetic vasomotor tone and AP and will determine functional changes that occur with chronic baroreceptor denervation and spontaneous hypertension. [unreadable] [unreadable]
Effective start/end date3/05/0431/05/16


  • National Heart, Lung, and Blood Institute


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