Carotid Body: The Primary Peripheral Arterial Chemoreceptor.

The carotid body (CB) is a polymodal chemosensory organ that plays an essential role in initiating respiratory and cardiovascular adjustments to maintain blood gas homeostasis. Much of the available evidence suggests that chronic hypoxia induces marked morphological and neurochemical changes within the CB, but the detailed molecular mechanisms by which these affect the hypoxic chemosensitivity still remain to be elucidated. Dysregulation of the CB function and altered oxygen saturation are implicated in various physiological and pathophysiological conditions. Knowledge of the morphological and functional aspects of the CB would improve our current understanding of respiratory and cardiovascular homeostasis in health and disease.

The Potential of Hydrogen Sulfide Donors in Treating Cardiovascular Diseases.

Hydrogen sulfide (H2S) has long been considered as a toxic gas, but as research progressed, the idea has been updated and it has now been shown to have potent protective effects at reasonable concentrations. H2S is an endogenous gas signaling molecule in mammals and is produced by specific enzymes in different cell types. An increasing number of studies indicate that H2S plays an important role in cardiovascular homeostasis, and in most cases, H2S has been reported to be downregulated in cardiovascular diseases (CVDs). Similarly, in preclinical studies, H2S has been shown to prevent CVDs and improve heart function after heart failure. Recently, many H2S donors have been synthesized and tested in cellular and animal models. Moreover, numerous molecular mechanisms have been proposed to demonstrate the effects of these donors. In this review, we will provide an update on the role of H2S in cardiovascular activities and its involvement in pathological states, with a special focus on the roles of exogenous H2S in cardiac protection.

C1 neurons: a nodal point for stress?

NEW FINDINGS: What is the topic of this review? The C1 neurons (C1) innervate sympathetic and parasympathetic preganglionic neurons plus numerous brain nuclei implicated in stress, arousal and autonomic regulations. We consider here the contribution of C1 to stress-induced responses. What advances does it highlight? C1 activation is required for blood pressure stability during hypoxia and mild hemorrhage which exemplifies their homeostatic function. During restraint stress, C1 activate the splenic anti-inflammatory pathway resulting in tissue protection against ischemic injury. This effect, along with glucose release and, possibly, arousal are examples of adaptive non-homeostatic responses to stress that are also mediated by C1. The C1 cells are catecholaminergic and glutamatergic neurons located in the rostral ventrolateral medulla. Collectively, these neurons innervate sympathetic and parasympathetic preganglionic neurons, the hypothalamic paraventricular nucleus and countless brain structures involved in autonomic regulation, arousal and stress. Optogenetic inhibition of rostral C1 neurons has little effect on blood pressure (BP) at rest in conscious rats but produces large reductions in BP when the animals are anaesthetized or exposed to hypoxia. Optogenetic C1 stimulation increases BP and produces arousal from non-rapid eye movement sleep. C1 cell stimulation mimics the effect of restraint stress to attenuate kidney injury caused by renal ischaemia-reperfusion. These effects are mediated by the sympathetic nervous system through the spleen and eliminated by silencing the C1 neurons. These few examples illustrate that, depending on the nature of the stress, the C1 cells mediate adaptive responses of a homeostatic or allostatic nature.

The Vascular Wall: a Plastic Hub of Activity in Cardiovascular Homeostasis and Disease.

PURPOSE OF REVIEW: This review aims to summarize recent findings regarding the plasticity and fate switching among somatic and progenitor cells residing in the vascular wall of blood vessels in health and disease. RECENT FINDINGS: Cell lineage tracing methods have identified multiple origins of stem cells, macrophages, and matrix-producing cells that become mobilized after acute or chronic injury of cardiovascular tissues. These studies also revealed that in the disease environment, resident somatic cells become plastic, thereby changing their stereotypical identities to adopt proinflammatory and profibrotic phenotypes. Currently, the functional significance of this heterogeneity among reparative cells is unknown. Furthermore, mechanisms that control cellular plasticity and fate decisions in the disease environment are poorly understood. Cardiovascular diseases are responsible for the majority of deaths worldwide. From a therapeutic perspective, these novel discoveries may identify new targets to improve the repair and regeneration of the cardiovascular system.

Anti-Atherogenic Properties of Allium ursinum Liophylisate: Impact on Lipoprotein Homeostasis and Cardiac Biomarkers in Hypercholesterolemic Rabbits.

The present investigation evaluates the capacity of Allium ursinum (wild garlic) leaf lyophilisate (WGLL; alliin content: 0.261%) to mitigate cardiovascular damage in hypercholesterolemic rabbits. New Zealand rabbits were divided into three groups: (i) cholesterol-free rabbit chow (control); (ii) rabbit chow containing 2% cholesterol (hypercholesterolemic, HC); (iii) rabbit chow containing 2% cholesterol + 2% WGLL (hypercholesterolemic treated, HCT); for eight weeks. At the zero- and eight-week time points, echocardiographic measurements were made, along with the determination of basic serum parameters. Following the treatment period, after ischemia-reperfusion injury, hemodynamic parameters were measured using an isolated working heart model. Western blot analyses of heart tissue followed for evaluating protein expression and histochemical study for the atheroma status determination. WGLL treatment mediated increases in fractional shortening; right ventricular function; peak systolic velocity; tricuspidal annular systolic velocity in live animals; along with improved aortic and coronary flow. Western blot analysis revealed WGLL-associated increases in HO-1 protein and decreases in SOD-1 protein production. WGLL-associated decreases were observed in aortic atherosclerotic plaque coverage, plasma ApoB and the activity of LDH and CK (creatine kinase) in plasma. Plasma LDL was also significantly reduced. The results clearly demonstrate that WGLL has complex cardioprotective effects, suggesting future strategies for its use in prevention and therapy for atherosclerotic disorders.

The acute adaptation of skin microcirculatory perfusion in vivo does not involve a local response but rather a centrally mediated adaptive reflex.

Introduction: Cardiovascular homeostasis involves the interaction of multiple players to ensure a permanent adaptation to each organ's needs. Our previous research suggested that changes in skin microcirculation-even if slight and distal-always evoke an immediate global rather than "local" response affecting hemodynamic homeostasis. These observations question our understanding of known reflexes used to explore vascular physiology, such as reactive hyperemia and the venoarteriolar reflex (VAR). Thus, our study was designed to further explore these responses in older healthy adults of both sexes and to potentially provide objective evidence of a centrally mediated mechanism governing each of these adaptive processes. Methods: Participants (n = 22, 52.5 ± 6.2 years old) of both sexes were previously selected. Perfusion was recorded in both feet by laser Doppler flowmetry (LDF) and photoplethysmography (PPG). Two different maneuvers with opposite impacts on perfusion were applied as challengers to single limb reactive hyperemia evoked by massage and a single leg pending to generate a VAR. Measurements were taken at baseline (Phase I), during challenge (Phase II), and recovery (Phase III). A 95% confidence level was adopted. As proof of concept, six additional young healthy women were selected to provide video imaging by using optoacoustic tomography (OAT) of suprasystolic post-occlusive reactive hyperemia (PORH) in the upper limb. Results: Modified perfusion was detected by LDF and PPG in both limbs with both hyperemia and VAR, with clear systemic hemodynamic changes in all participants. Comparison with data obtained under the same conditions in a younger cohort, previously published by our group, revealed that results were not statistically different between the groups. Discussion: The OAT documentary and analysis showed that the suprasystolic pressure in the arm changed vasomotion in the forearm, displacing blood from the superficial to the deeper plexus vessels. Deflation allowed the blood to return and to be distributed in both plexuses. These responses were present in all individuals independent of their age. They appeared to be determined by the need to re-establish hemodynamics acutely modified by the challenger, which means that they were centrally mediated. Therefore, a new mechanistic interpretation of these exploratory maneuvers is required to better characterize in vivo cardiovascular physiology in humans.

Sex Differences and Regulatory Actions of Estrogen in Cardiovascular System.

Great progress has been made in the understanding of the pathophysiology of cardiovascular diseases (CVDs), and this has improved the prevention and prognosis of CVDs. However, while sex differences in CVDs have been well documented and studied for decades, their full extent remains unclear. Results of the latest clinical studies provide strong evidence of sex differences in the efficacy of drug treatment for heart failure, thereby possibly providing new mechanistic insights into sex differences in CVDs. In this review, we discuss the significance of sex differences, as rediscovered by recent studies, in the pathogenesis of CVDs. First, we provide an overview of the results of clinical trials to date regarding sex differences and hormone replacement therapy. Then, we discuss the role of sex differences in the maintenance and disruption of cardiovascular tissue homeostasis.

Identification of a population of peripheral sensory neurons that regulates blood pressure.

The vasculature is innervated by a network of peripheral afferents that sense and regulate blood flow. Here, we describe a system of non-peptidergic sensory neurons with cell bodies in the spinal ganglia that regulate vascular tone in the distal arteries. We identify a population of mechanosensitive neurons, marked by tropomyosin receptor kinase C (TrkC) and tyrosine hydroxylase in the dorsal root ganglia, which projects to blood vessels. Local stimulation of TrkC neurons decreases vessel diameter and blood flow, whereas systemic activation increases systolic blood pressure and heart rate variability via the sympathetic nervous system. Ablation of the neurons provokes variability in local blood flow, leading to a reduction in systolic blood pressure, increased heart rate variability, and ultimately lethality within 48 h. Thus, a population of TrkC+ sensory neurons forms part of a sensory-feedback mechanism that maintains cardiovascular homeostasis through the autonomic nervous system.

Vasopressin in Heart Failure.

BACKGROUND AND OBJECTIVE: The nonapeptide hypothalamic hormone vasopressin (VP), exerts important effects on cardiovascular system via its receptors V1, V2 and V3. Patients with congestive heart failure (CHF) present elevated plasma VP levels. Aim of this paper is to review the role of vasopressin in CHF. METHODS: We analyzed the best of published literature dealing with the role of VP in patients affected by CHF, identifying keywords and MeSH terms in Pubmed and then searching them. The last search was performed on August 2017. RESULTS: Scientific articles dealing with the relationship between VP and CHF show that circulating high VP levels found in CHF despite an exaggerated increase in circulatory blood volume can contribute to CHF exacerbation. In particular, the stimulation of V1R induces vascular constriction responsible for increased systemic vascular resistance and afterload, and, in addition, coronary vasoconstriction with consequent reduced coronary circulation and cardiac contractility, whereas the stimulation of V2R induces free water reabsorption and this is responsible of preload increase and congestion of pulmonary vascular bed with edema and hyponatremia, markers of advanced CHF. CONCLUSION: VP can play an important role among the derangements of the endocrine system in CHF even being a possible target in the treatment of this condition. Vaptans, antagonists of VP receptors, in fact, are able to increase urine output and plasma sodium levels without the increased risk of arrhythmic death induced by diuretics, even though, further studies are needed to establish a possible role of these drugs in the treatment of CHF.

The human cortical autonomic network and volitional exercise in health and disease.

The autonomic nervous system elicits continuous beat-by-beat homeostatic adjustments to cardiovascular control. These modifications are mediated by sensory inputs (e.g., baroreceptors, metaboreceptors, pulmonary, thermoreceptors, and chemoreceptors afferents), integration at the brainstem control centres (i.e., medulla), and efferent autonomic neural outputs (e.g., spinal, preganglionic, and postganglionic pathways). However, extensive electrical stimulation and functional imaging research show that the brain's higher cortical regions (e.g., insular cortex, medial prefrontal cortex, anterior cingulate cortex) partake in homeostatic regulation of the cardiovascular system at rest and during exercise. We now appreciate that these cortical areas form a network, namely the "cortical autonomic network" (CAN), which operate as part of a larger central autonomic network comprising 2-way communication of cortical and subcortical areas to exert autonomic influence. Interestingly, differential patterns of CAN activity and ensuing cardiovascular control are present in disease states, thereby highlighting the importance of considering the role of CAN as an integral aspect of cardiovascular regulation in health and disease. This review discusses current knowledge on human cortical autonomic activation during volitional exercise, and the role of exercise training on this activation in both health and disease.

Mathematical modelling of cardiovascular response to the Valsalva manoeuvre.

The Valsalva manoeuvre (VM) used for clinical autonomic testing results in a complex cardiovascular response with a concomitant action of several regulatory mechanisms whose nonlinear interactions are difficult to analyse without the aid of a mathematical model. The article presents a new non-pulsatile compartmental model of the human cardiovascular system with a variable intrathoracic pressure enabling the simulation of the haemodynamic response to the VM. The model is based on physiological data and includes three baroreflex mechanisms acting on heart rate, systemic resistance and venous unstressed volume. New nonlinear functions have been proposed to model cardiac output dependence on preload and afterload. Following the individual fitting of some parameters with a clear physiological meaning, the model is able to fit clinical data from patients with both typical and abnormal haemodynamic response to the VM. The sensitivity analysis showed that the model is most sensitive to the parameters describing the vascular pressure-volume relationships (the maximal volume of systemic veins and the relative level of vascular compliance). The use of nonlinear pressure-volume relationships for systemic veins proved crucial for the accurate modelling of the VM. On the contrary, the introduction of aroreflex time delays did not change significantly the haemodynamic response to the manoeuvre. The model can be a useful tool for aiding the interpretation of patient's response to the VM and provides a framework for analysing the interactions between the cardiovascular system and autonomic regulatory mechanisms.

Recent advances in central cardiovascular control: sex, ROS, gas and inflammation.

The central nervous system (CNS) in concert with the heart and vasculature is essential to maintaining cardiovascular (CV) homeostasis. In recent years, our understanding of CNS control of blood pressure regulation (and dysregulation leading to hypertension) has evolved substantially to include (i) the actions of signaling molecules that are not classically viewed as CV signaling molecules, some of which exert effects at CNS targets in a non-traditional manner, and (ii) CNS locations not traditionally viewed as central autonomic cardiovascular centers. This review summarizes recent work implicating immune signals and reproductive hormones, as well as gasotransmitters and reactive oxygen species in the pathogenesis of hypertension at traditional CV control centers. Additionally, recent work implicating non-conventional CNS structures in CV regulation is discussed.