Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The long-term level of arterial pressure is dependent on the relationship between arterial pressure and the urinary output of salt and water, which, in turn, is affected by a number of factors, including renal sympathetic nerve activity (RSNA). In the present brief review, we consider the mechanisms within the brain that can influence RSNA, focusing particularly on hypothalamic mechanisms. 2. The paraventricular nucleus (PVN) in the hypothalamus has major direct and indirect connections with the sympathetic outflow and there is now considerable evidence that tonic activation of the PVN sympathetic pathway contributes to the sustained increased level of RSNA that occurs in conditions such as heart failure and neurogenic hypertension. The tonic activity of PVN sympathetic neurons, in turn, depends upon the balance of excitatory and inhibitory inputs. A number of neurotransmitters and neuromodulators are involved in these tonic excitatory and inhibitory effects, including glutamate, GABA, angiotensin II and nitric oxide. 3. The dorsomedial hypothalamic nucleus (DMH) also exerts a powerful influence over sympathetic activity, including RSNA, via synapses with sympathetic nuclei in the medulla and, possibly, also other brainstem regions. The DMH sympathetic pathway is an important component of the phasic sympathoexcitatory responses associated with acute stress, but there is no evidence that it is an important component of the central pathways that produce long-term changes in arterial pressure. Nevertheless, it is possible that repeated episodic activation of this pathway could lead to vascular hypertrophy and, thus, sustained changes in vascular resistance and arterial pressure. 4. Recent studies have reactivated the old debate concerning the possible role of the baroreceptor reflex in the long-term regulation of sympathetic activity. Therefore, central resetting of the baroreceptor-sympathetic reflex may be an important component of the mechanisms causing sustained changes in RSNA. However, little is known about the cellular mechanisms that could cause such resetting.
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PMID:Long-term regulation of arterial blood pressure by hypothalamic nuclei: some critical questions. 1585 52

1. The role of cytokines in cardiovascular control, especially in neurogenic hypertension, has received considerable attention during the past few years. Brain cytokines have been shown to exert profound effects on neuronal activity. Recently, a number of studies have shown that administration of pro-inflammatory cytokines or anti-inflammatory cytokines into the central nervous system has a significant impact on sympathetic outflow, arterial pressure and cardiac remodelling in experimental models of hypertension and heart failure. 2. Our objective in this review is to present a succinct account of the effect of cytokines on neuronal activity and their role in cardiovascular disease. Furthermore, we propose a hypothesis for a neuromodulatory role of cytokines in the neural control of cardiovascular function.
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PMID:Brain cytokines as neuromodulators in cardiovascular control. 1956 37

Cardiac sympathetic overactivity is a well-established contributor to the progression of neurogenic hypertension and heart failure, yet the underlying pathophysiology remains unclear. Recent studies have highlighted the importance of acutely regulated cyclic nucleotides and their effectors in the control of intracellular calcium and exocytosis. Emerging evidence now suggests that a significant component of sympathetic overactivity and enhanced transmission may arise from impaired cyclic nucleotide signalling, resulting from compromised phosphodiesterase activity, as well as alterations in receptor-coupled G-protein activation. In this review, we address some of the key cellular and molecular pathways that contribute to sympathetic overactivity in hypertension and discuss their potential for therapeutic targeting.
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PMID:Neurocardiac regulation: from cardiac mechanisms to novel therapeutic approaches. 3030 15

The carotid body (CB) is an important organ located at the carotid bifurcation that constantly monitors the blood supplying the brain. During hypoxia, the CB immediately triggers an alarm in the form of nerve impulses sent to the brain. This activates protective reflexes including hyperventilation, tachycardia and vasoconstriction, to ensure blood and oxygen delivery to the brain and vital organs. However, in certain conditions, including obstructive sleep apnea, heart failure and essential/spontaneous hypertension, the CB becomes hyperactive, promoting neurogenic hypertension and arrhythmia. G-protein-coupled receptors (GPCRs) are very highly expressed in the CB and have key roles in mediating baseline CB activity and hypoxic sensitivity. Here, we provide a brief overview of the numerous GPCRs that are expressed in the CB, their mechanism of action and downstream effects. Furthermore, we will address how these GPCRs and signaling pathways may contribute to CB hyperactivity and cardiovascular and respiratory disease. GPCRs are a major target for drug discovery development. This information highlights specific GPCRs that could be targeted by novel or existing drugs to enable more personalized treatment of CB-mediated cardiovascular and respiratory disease.
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PMID:G-Protein-Coupled Receptor (GPCR) Signaling in the Carotid Body: Roles in Hypoxia and Cardiovascular and Respiratory Disease. 3282 27