No abstract

C hronic elevation in sympathetic nerve activity (SNA) is associated with the development and maintenance of certain types of hypertension 1 and contributes to the progression of chronic heart failure (CHF). 2 The mechanisms involved in sympathetic dysfunction in these disorders appear to be complex and multifactorial. A unified hypothesis is likely to encompass alterations in multiple autonomic reflex pathways, central integratory sites, and chemical mediators that control sympathetic outflow. For example, tonic restraint of sympathetic outflow by arterial and cardiopulmonary baroreflexes is depressed in CHF 2 and depressed or reset in hypertension. 3 Moreover, maladaptive changes also occur in the central nervous system at integrative sites for autonomic control in both disease processes. 4,5 It is also clear that sympathoexcitatory cardiac, 6 somatic, 7 and central/peripheral chemoreceptor reflexes 8 are enhanced in CHF and hypertension.Arterial chemoreceptors serve an important regulatory role in the control of alveolar ventilation, but they also exert a powerful influence on cardiovascular function. 9 Activation of arterial chemoreceptors by hypoxemia increases sympathetic outflow to systemic vascular beds to compensate for the direct vasodilating effects of hypoxia on these vessels and to redistribute blood flow to essential organs. In this review, we highlight relevant information that implicates the arterial chemoreflex as a contributory mechanism for the sympathetic hyperactivity in CHF and hypertension and illustrate proposed mechanisms for this altered function. The Sympathetic Response to Arterial Chemoreceptor ActivationArterial chemoreceptors located in the aortic and carotid bodies (CBs) respond to hypoxemia and hypercapnia. Because central chemoreceptors also respond to hypercapnia, hypoxia is typically used as a specific stimulus to arterial chemoreceptors. In some mammals, such as rats and rabbits, reflex responses to hypoxemia arise solely from the CB, whereas in other species, the aortic chemoreceptor contribution can be significant. However, it is not possible to experimentally separate the relative contribution of the aortic and CBs to reflex responses in conscious animals or humans. For these reasons, discussions on the arterial chemoreflex generally relate functionality to that of the CB, which has been more extensively studied. Glomus cells in the CB depolarize in response to hypoxia and release multiple putative neurotransmitters (including acetylcholine, serotonin, ATP, and substance P) that activate impulses in afferent fibers traveling to the medulla via the carotid sinus nerve. 10 Arterial chemoreceptor stimulation in freely breathing humans and conscious animals increases sympathetic vasoconstrictor outflow to muscle, splanchnic, and renal beds to elevate arterial pressure, and, in humans, increases cardiac sympathetic activity to increase heart rate and contractility. 9 There is preferential activation of sympathetic fibers going to the adrenal gland to increase norepinephrine but...

An analytical study of diffusiophoresis in a homogeneous suspension of identical spherical charge-regulating particles with an arbitrary thickness of the electric double layers in a solution of a symmetrically charged electrolyte with a uniform prescribed concentration gradient is presented. The charge regulation due to association/dissociation reactions of ionogenic functional groups on the particle surface is approximated by a linearized regulation model, which specifies a linear relationship between the surface charge density and the surface potential. The effects of particle-particle electrohydrodynamic interactions are taken into account by employing a unit cell model, and the overlap of the double layers of adjacent particles is allowed. The electrokinetic equations that govern the electric potential profile, the ionic concentration distributions, and the fluid flow field in the electrolyte solution surrounding the particle in a unit cell are linearized assuming that the system is only slightly distorted from equilibrium. Using a regular perturbation method, these linearized equations are solved with the equilibrium surface charge density (or zeta potential) of the particle as the small perturbation parameter. Closed-form formulas for the diffusiophoretic velocity of the charge-regulating sphere correct to the second order of its surface charge density or zeta potential are derived. Our results indicate that the charge regulation effect on the diffusiophoretic mobility is quite sensitive to the boundary condition for the electric potential specified at the outer surface of the unit cell. For the limiting cases of a very dilute suspension and a very thin or very thick electric double layer, the particle velocity is independent of the charge regulation parameter.