ROLE OF OLFACTORY RECEPTOR78 IN CAROTID BODY DEPENDENT SYMPATHETIC ACTIVATION AND HYPERTENSION IN MURINE MODELS OF CHRONIC INTERMITTENT HYPOXIA

2021 ◽  
Author(s):  
Ying-Jie Peng ◽  
Xiaoyu Su ◽  
Benjamin L Wang ◽  
Timothy David Matthews ◽  
Jayasri Nanduri ◽  
...  
Keyword(s):  
Nervous System ◽  
Sympathetic Nervous System ◽  
Carotid Body ◽  
Intermittent Hypoxia ◽  
Sensory Nerve ◽  
Chronic Intermittent Hypoxia ◽  
Murine Models ◽  
Nerve Response ◽  
Sympathetic Nervous ◽  
Sympathetic Nerve Activation

Chronic intermittent hypoxia (CIH) is a hallmark manifestation of obstructive sleep apnea (OSA), a widespread breathing disorder. CIH treated rodents exhibit activation of the sympathetic nervous system and hypertension. Heightened carotid body (CB) activity has been implicated in CIH-induced hypertension. CB expresses high abundance of olfactory receptor (Olfr) 78, a G-protein coupled receptor. Olfr 78 null mice exhibit impaired CB sensory nerve response to acute hypoxia. Present study examined whether Olfr78 participates in CB-dependent activation of the sympathetic nervous system and hypertension in CIH treated mice and in hemeoxygenase (HO)-2 null mice experiencing CIH as a consequence of naturally occurring OSA. CIH treated wild type (WT) mice showed hypertension, bio-markers of sympathetic nerve activation, and enhanced CB sensory nerve response to hypoxia and sensory long-term facilitation (sLTF), and these responses were absent in CIH treated Olfr78 null mice. HO-2 null mice showed higher apnea index (AI) (58±1.2 apneas/hour) than WT mice (AI= 8±0.8 apneas/hour), and exhibited elevated blood pressure (BP), plasma NE levels and heightened CB sensory nerve response to hypoxia and sLTF. The magnitude of hypertension correlated with AI in HO-2 null mice. In contrast, HO-2/Olfr78 double null mice showed absence of elevated BP, plasma NE levels, augmented CB response to hypoxia and sLTF. These results demonstrate that Olfr78 participates in sympathetic nerve activation and hypertension, and heightened CB activity in two murine models of CIH.

scholarly journals Roles of Beta2- and Beta3-Adrenoceptor Polymorphisms in Hypertension and Metabolic Syndrome

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Kazuko Masuo
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Syndrome ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Vascular Reactivity ◽  
Resting Metabolic Rate ◽  
Sympathetic Nervous ◽  
Obesity Hypertension ◽  
Sympathetic Nerve Activation

Hypertension, diabetes mellitus (especially type 2 diabetes mellitus), metabolic syndrome and obesity are rapidly growing public health problems. Sympathetic nerve activation is observed in obesity, hypertension and diabetes mellitus, which have strong genetic as well as environmental determinants. Reduced energy expenditure and resting metabolic rate are predictive of weight gain, and the sympathetic nervous system participates in regulating energy balance through thermogenesis. The thermogenic effects of catecholamines in obesity have been mainly mediated via the 2- and 3-adrenergic receptors in humans. Further, 2-adrenoceptors importantly influence vascular reactivity and may regulate blood pressure. Genetic polymorphistns of the -adrenoceptor gene have been shown to alter the function of several adrenoceptor subtypes and thus to modify the response to catecholamine. 2-adrenoceptor polymorphisms (Arg16Gly, Gln27Glu, and Thr164Ile) have been studied in relation to hypertension. Genetic variations in the 3-adrenoceptor (i.e. Try64Arg variant) are also associated with both obesity and hypertension. However, the precise relationships of the polymorphisms of 2- and 3-adrenoceptor genes with sympathetic nervous system activity, hypertension, and metabolic syndrome have not been fully clarified. This paper will discuss the current topics involving the influence of the sympathetic nervous system and 2- and 3- adrenoceptor polymorphisms in hypertension and metabolic syndrome.

scholarly journals Leptin receptor-expressing neuron Sh2b1 supports sympathetic nervous system and protects against obesity and metabolic disease

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Lin Jiang ◽  
Haoran Su ◽  
Xiaoyin Wu ◽  
Hong Shen ◽  
Min-Hyun Kim ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Leptin Receptor ◽  
Core Body Temperature ◽  
Liver Steatosis ◽  
Adult Onset ◽  
Brown Adipose ◽  
Sympathetic Nervous ◽  
Sympathetic Nerve Activation

Abstract Leptin stimulates the sympathetic nervous system (SNS), energy expenditure, and weight loss; however, the underlying molecular mechanism remains elusive. Here, we uncover Sh2b1 in leptin receptor (LepR) neurons as a critical component of a SNS/brown adipose tissue (BAT)/thermogenesis axis. LepR neuron-specific deletion of Sh2b1 abrogates leptin-stimulated sympathetic nerve activation and impairs BAT thermogenic programs, leading to reduced core body temperature and cold intolerance. The adipose SNS degenerates progressively in mutant mice after 8 weeks of age. Adult-onset ablation of Sh2b1 in the mediobasal hypothalamus also impairs the SNS/BAT/thermogenesis axis; conversely, hypothalamic overexpression of human SH2B1 has the opposite effects. Mice with either LepR neuron-specific or adult-onset, hypothalamus-specific ablation of Sh2b1 develop obesity, insulin resistance, and liver steatosis. In contrast, hypothalamic overexpression of SH2B1 protects against high fat diet-induced obesity and metabolic syndromes. Our results unravel an unrecognized LepR neuron Sh2b1/SNS/BAT/thermogenesis axis that combats obesity and metabolic disease.

scholarly journals Neural regulation of hypoxia-inducible factors and redox state drives the pathogenesis of hypertension in a rodent model of sleep apnea

2015 ◽  
Vol 119 (10) ◽  
pp. 1152-1156 ◽  
Author(s):  
Gregg L. Semenza ◽  
Nanduri R. Prabhakar
Keyword(s):  
Nervous System ◽  
Sleep Apnea ◽  
Sympathetic Nervous System ◽  
Brain Stem ◽  
Carotid Body ◽  
Sympathetic Neurons ◽  
Ventrolateral Medulla ◽  
Obstructive Sleep ◽  
Sympathetic Nervous ◽  
The Brain

Obstructive sleep apnea (OSA) is one of the most common causes of hypertension in western societies. OSA causes chronic intermittent hypoxia (CIH) in specialized O2-sensing glomus cells of the carotid body. CIH generates increased reactive oxygen species (ROS) that trigger a feedforward mechanism in which increased intracellular calcium levels ([Ca2+]i) trigger increased HIF-1α synthesis and increased HIF-2α degradation. As a result, the normal homeostatic balance between HIF-1α-dependent prooxidant and HIF-2α-dependent antioxidant enzymes is disrupted, leading to further increases in ROS. Carotid body sensory nerves project to the nucleus tractus solitarii, from which the information is relayed via interneurons to the rostral ventrolateral medulla in the brain stem, which sends sympathetic neurons to the adrenal medulla to stimulate the release of epinephrine and norepinephrine, catecholamines that increase blood pressure. At each synapse, neurotransmitters trigger increased [Ca2+]i, HIF-1α:HIF-2α, and Nox2:Sod2 activity that generates increased ROS levels. These responses are not observed in other regions of the brain stem that do not receive input from the carotid body or signal to the sympathetic nervous system. Thus sympathetic nervous system homeostasis is dependent on a balance between HIF-1α and HIF-2α, disruption of which results in hypertension in OSA patients.

Cervical preganglionic sympathetic nerve activity and chemoreflexes in the cat

1987 ◽  
Vol 62 (4) ◽  
pp. 1713-1720 ◽  
Author(s):  
S. Matsumoto ◽  
A. Mokashi ◽  
S. Lahiri
Keyword(s):  
Nervous System ◽  
Steady State ◽  
Sympathetic Nervous System ◽  
Carotid Body ◽  
Sympathetic Nerve ◽  
Base Line ◽  
Respiratory Drive ◽  
Steady State Levels ◽  
Sympathetic Nervous ◽  
Arterial Po2

The role of chemoreflexes originating from carotid body and central chemoreceptors in the regulation of cervical preganglionic sympathetic nerve (PSN) activity was studied in anesthetized and spontaneously breathing cats. PSN efferents which responded to hypoxia were selected for the study. The PSN activity, breath-by-breath inspiratory tidal volume, tracheal PO2 and PCO2, and arterial systemic blood pressure were recorded simultaneously. The responses of PSN efferents to transient changes in and steady-state levels of arterial PO2 and PCO2 and to graded bolus injections of intravenous sodium cyanide (50–100 micrograms), nicotine (50–100 micrograms), and dopamine hydrochloride (30–60 micrograms) were compared before and after bilateral section of carotid sinus nerves (CSN). CSN section raised the base-line PSN activity and practically eliminated the responses to brief pharmacological stimuli, but it did not eliminate the responses to transient changes in and steady-state levels of arterial PO2 and PCO2. However, CSN section diminished PSN responses and abolished ventilatory responses to hypoxia. Thus the PSN response to hypoxia was partly independent of peripheral chemoreflex and of respiratory drive. We conclude that carotid body chemoreflex elicits fast PSN responses and that a moderate decline in arterial PO2 causes an additional slow, direct excitation of sympathetic nervous system. The latter indicates O2 chemosensitivity of the system in the physiological range of arterial PO2. This O2-sensing property may allow sympathetic nervous system to initiate chemoreflex responses independent of the peripheral chemoreceptors.

Thyroid hormone-catecholamine interrelationships during exposure to cold

1981 ◽  
Vol 97 (1) ◽  
pp. 91-97 ◽  
Author(s):  
H. Storm ◽  
C. van Hardeveld ◽  
A. A. H. Kassenaar
Keyword(s):  
Nervous System ◽  
Plasma Concentration ◽  
Thyroid Hormone ◽  
Sympathetic Nervous System ◽  
Plasma Levels ◽  
Surgical Procedure ◽  
Exposure To Cold ◽  
Basal Plasma ◽  
Sympathetic Nervous

Abstract. Basal plasma levels for adrenalin (A), noradrenalin (NA), l-triiodothyronine (T3), and l-thyroxine (T4) were determined in rats with a chronically inserted catheter. The experiments described in this report were started 3 days after the surgical procedure when T3 and T4 levels had returned to normal. Basal levels for the catecholamines were reached already 4 h after the operation. The T3/T4 ratio in plasma was significantly increased after 3, 7, and 14 days in rats kept at 4°C and the same holds for the iodide in the 24-h urine after 7 and 14 days at 4°C. The venous NA plasma concentration was increased 6- to 12-fold during the same period of exposure to cold, whereas the A concentration remained at the basal level. During infusion of NA at 23°C the T3/T4 ratio in plasma was significantly increased after 7 days compared to pair-fed controls, and the same holds for the iodide excretion in the 24-h urine. This paper presents further evidence for a role of the sympathetic nervous system on T4 metabolism in rats at resting conditions.

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