Gustatory and interoceptive regulation of hypertension

高血压的味觉和内感受调节

• 批准号: 10608950
• 负责人: Caitlin Marie Baumer Harrison
• 金额: $ 2.87万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10608950
• 关键词: Ablation; Acetates; Affect; Angiotensin II; Angiotensin Type 1a Receptor; Angiotensins; Attenuated; Baroreflex; Blood Pressure; Blood Volume; Brain; Brain Stem; Brain region; Cardiovascular Diseases; Cardiovascular Physiology; Cardiovascular system; Cause of Death; Consumption; Cre lox recombination system; DOCA; Deoxycorticosterone; Desire for food; Detection; Development; Disease; Esthesia; Etiology; Fluid Balance; Foundations; Frequencies; Ganglia; Gene Transfer; Goals; Health; Heart; Hypertension; Impairment; Intake; Interoception; Kidney; Knowledge; Link; Mediating; Modeling; Mus; Nerve; Neuroanatomy; Neurons; Nucleus solitarius; Nutrient; Peptides; Perception; Peripheral; Physiological; Physiological Processes; Play; Population; Positioning Attribute; Pressoreceptors; Prevention; Process; Regulation; Research; Role; Scientist; Sensory; Signal Transduction; Sodium; Sodium Chloride; Stretching; Taste Bud Cell; Taste Buds; Taste Perception; Testing; Tissues; Tongue; Toxin; Training; Viral; Work; blood pressure reduction; blood pressure regulation; cardiovascular disorder risk; cardiovascular risk factor; experimental study; extracellular; hypertension treatment; hypertensive; in vivo; insight; neuronal excitability; neurotransmission; normotensive; novel; optogenetics; peptide hormone; pressure; receptor; salt sensitive hypertension; sensory integration; sensory system; taste system

PROJECT SUMMARY The overconsumption of sodium (Na+) is a major health problem in the U.S. and around the world, having been linked to many health conditions, including hypertension—a major risk factor for cardiovascular disease. While the relationship between Na+-intake and hypertension is widely recognized, the mechanism(s) behind this relationship are not well understood. The proposed experiments aim to delineate the mechanism(s) underlying this relationship by investigating sensory systems that regulate Na+-taste/intake and blood pressure (BP). My preliminary studies conducted in mice discovered that neurons within the nodose and petrosal ganglion that express the angiotensin type 1a receptor (NPGAT1aR) send afferents to the nucleus of the solitary tract (NTS). The NPG contains neurons that function as baroreceptors that sense blood pressure or as gustatory afferents that transduce Na+-taste. Intriguingly, optogenetic excitation of afferents in the NTS arising from NPGAT1aR significantly reduces blood pressure and Na+-intake. Moreover, mice overconsuming NaCl solutions and rendered hypertensive via deliver of deoxycorticosterone acetate (DOCA-salt) required greater frequencies of stimulation to lower blood pressure relative to normotensive mice. Collectively, my preliminary results suggest that the NPGAT1aR send afferents to the NTS that mediate the interoception of blood pressure and the perception of Na+-taste and the excitability of these neurons can be used to study the etiology of hypertension that follows Na+ overconsumption. Accordingly, I have developed the overall hypothesis that NPGAT1aR send afferents to the NTS that regulate blood pressure and Na+-intake, and that AT1aR(s) on these neurons contribute to the development of DOCA- salt hypertension. To confirm or refute this hypothesis, I will address the following aims. Aim 1 will use neuroanatomical characterizations and optogenetic activation of NPGAT1aR afferents in the rostral and caudal NTS to determine whether the connectivity and excitation of these afferents are sufficient to alter Na+-intake and blood pressure under basal conditions and following depletion of blood volume. Aim 2 will use Cre-LoxP system and virally-mediated gene transfer to selectively delete AT1aR(s) from the NPG to determine whether these AT1aR are necessary for increased Na+-intake and decreased baroreflex sensitivity that accompany the DOCA-salt model of hypertension. Collectively, these experiments will shed light on gustatory and interoceptive integration in the brainstem to better understand the relationship between Na+-intake and blood pressure regulation, thereby providing novel insight that can be leveraged to develop treatments for hypertension.

项目总结