The central nervous system is important in the regulation of arterial pressure and an abundance of data suggests that the brain plays a critical role in the pathogenesis of some forms of hypertension. Several previous studies have suggested that an attenuation of the baroreceptor reflex occurring within the central nervous system contributes to the development of certain forms of experimental hypertension. The nucleus tractus solitarius (NTS) is the site in the brain which receives all of the input from peripheral baroreceptors, and therefore is prominently involved in the processing of the baroreceptor reflex. Recent data indicate that stimulation of GABA/B receptors in the NTS attenuates the baroreceptor reflex and that neural transmission mediated by GABA/B receptors in the NTS is abnormal in certain forms of experimental hypertension. Thus, the hypothesis is presented that enhanced GABA/B- mediated neural transmission in the NTS, by producing a central attenuation of the baroreceptor reflex, contributes to the pathogenesis of hypertension in two models of experimental hypertension, the spontaneously (genetic) hypertensive rat and the rat treated with deoxycorticosterone and salt. Studies described in this proposal examine this hypothesis by determining the relationship between changes in GABAB receptors in the NTS, GABA release in the NTS, cardiovascular responses to injection into the NTS of drugs which are agonists or antagonists at GABA/B receptors, and the development of hypertension. Additional studies will examine the mechanisms involved in this GABA/B-mediated attenuation of the baroreceptor reflex. The hypothesis to be tested is that GABA acting on GABA/B receptors present presynaptically on baroreceptor afferent nerves attenuates the release of neurotransmitter from baroreceptor afferents, and that this mechanism underlies the frequency-dependent inhibition of baroreceptor afferent transmission in the NTS. It is expected that these studies will increase our understanding of the central neural control of cardiovascular function as it relates to hypertension and may provide new insight into the treatment or prevention of hypertension.
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