Autonomic outflow

The diffuse nature of orexinergic projections is consistent with combined patterns of expression of the two orexin receptors, which is widespread but differential and often complementary within and even outside the CNS. OX2Rs are found primarily in structures attributed to control of sleq)-wake functions, whereas OXIRs are more abundant in limbic structures controlling aspects of feeding, autonomic outflow, energy homeostasis, and to a lesser extent also REM-sleq). 

Bohus B, Koolhaas JM, Luiten PG, Korte SM, Roozendaal B, Wiersma A (1996) The neurobiology of the central nucleus of the amygdala in relation to neuroendocrine and autonomic outflow. Prog Brain Res 107 447 60... 

GC exert their regulatory effects on the HPA system via two types of corticosteroid receptors the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) (Reul and De Kloet 1985). GRs occur everywhere in the brain but are most abundant in hypothalamic CRH neurons and pituitary corticotropes. MRs, in contrast, are highly expressed in the hippocampus and, at lower expression levels, in hypothalamic sites involved in the regulation of salt appetite and autonomic outflow. The MR binds GC with a tenfold higher affinity than does the GR (Reul and De Kloet 1985). These findings on corticosteroid receptor diversity led to the working hypothesis that the tonic influences of corticosterone... 

Nonopioid. The withdrawal sjmdrome is also treatable with nonopioid drugs. Lofexidine inhibits sympathetic autonomic outflow by its agonist action on central presynaptic cc -adrenoceptors and so reduces the effects of noradrenergic hyperactivity (see above). It is similar to clonidine (see p. 482) but less likely to cause hypotension. Evidence indicates that lofexidine is as effective as methadone in withdrawal supervised in residential or community settings having no street value it is not liable to be traded. 

The in vivo cardiovascular effects of carmabinoids are complex and may involve modulation of the autonomic outflow in both the central and peripheral nervous systems as well as direct effects on the myocardium and vasculature. However, their peripheral actions appear to play the dominant role, at least upon systemic administration at the doses used by most investigators. Moreover, the effects of endocannabinoids are complicated by their rapid metabolism, which may liberate other vasoactive substances and their precursors (reviewed in Mechoulam et al. 1998 Kunos et al. 2002 Randall et al. 2002 Ralevic et al. 2002). 

Saul, J. P. (1990). Beat-to-beat variations of heart rate reflect modulation of cardiac autonomic outflow. News in Physiological Science, 3,32-37. 

Patients with the following underlying conditions can be particularly sensitive to the actions of vasodilators, including sildenafil, tadalafil, and vardenafil Those with left ventricular outflow obstruction (eg, aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic control of blood pressure. 

In addition to the integrated participation of the peripheral nerves, central neural pathways are involved in the process. These central mechanisms interact during normal sexual activity and require complex coordination between the autonomic nervous system and the somatic outflow at the level of the spinal cord. 

Autonomic and hormonal control of cardiovascular function. Note that two feedback loops are present the autonomic nervous system loop and the hormonal loop. The sympathetic nervous system directly influences four major variables peripheral vascular resistance, heart rate, force, and venous tone. It also directly modulates renin production (not shown). The parasympathetic nervous system directly influences heart rate. In addition to its role in stimulating aldosterone secretion, angiotensin II directly increases peripheral vascular resistance and facilitates sympathetic effects (not shown). The net feedback effect of each loop is to compensate for changes in arterial blood pressure. Thus, decreased blood pressure due to blood loss would evoke increased sympathetic outflow and renin release. Conversely, elevated pressure due to the administration of a vasoconstrictor drug would cause reduced sympathetic outflow, reduced renin release, and increased parasympathetic (vagal) outflow. 

Hess s model is all the more prescient because, at the time of its articulation, the cellular and molecular neurobiology of the central instantiation of the two branches of the autonomic nervous system were completely unknown. He had to infer their existence from his knowledge of the peripheral system and from the effects of his manipulation of the brain upon their outflow. The breakthrough came only in the early 1960s, when Anica Dahlstrom, K]ell Euxe, and others identified the norepinephrine containing cells of the locus coeruleus and the serotonin containing cells of the midline raphe nucleus. And it was even later when Marcel Mesulam and others mapped the central cholinergic neuronal system. 

It is well established that increased sympathetic nerve activity is associated with chronic heart failure (CHF) (Porter et al. 1990 Singh 2000 Olshansky 2005 Brodde et al. 2006 Watson et al. 2006). The increase in sympathetic activity is a compensatory mechanism that provides inotropic support to the heart and peripheral vasoconstriction. However, it promotes disease progression and worsens prognosis (Watson et al. 2006). The autonomic nervous system (ANS) is a very complex, balanced system that influences the initiation, termination, and perpetuation of atrial fibrillation (AF), and the AF affects the ANS (Olshansky, 2005). At rest, sympathetic and parasympathetic outflows are related reciprocally heart failure patients had high sympathetic and low parasympathetic outflows, and healthy subjects had low sympathetic and high parasympathetic outflows (Porter et al. 1990). 

Purkinje cells is demonstrated in Figure 12.1 and, like all cardiac myocytes, can be divided into four phases. Phase 4 (pacemaker potential) involves the slow influx of sodium ions, depolarizing the cell until the threshold potential is reached. Once the threshold potential is reached, the fast sodium current is activated, resulting in a rapid influx of sodium ions causing cell depolarization (phase 0 rapid depolarization). Phase 1 (partial repolarization) involves the inactivation of sodium channels and a transient outward current. Phase 2 (plateau phase) results from the slow influx of calcium ions. Repolarization (phase 3) occurs as a result of outflow of potassium ions from the cell and restores the resting potential. There are variations between the different areas of the heart, specifically the nodal tissues do not possess fast sodium channels and slow L-t5rpe calcium channels generate phase 0 current (Fig. 12.1). Phase 4 activity varies between nodal areas the sinoatrial node depolarizes more rapidly than the atrioventricular (AV) node. Automaticity is under autonomic nervous system control. Parasympathetic neurons... 

Blood pressure is the product of total peripheral resistance (TPR) and cardiac output (CO). Both branches of the ANS are involved in the autonomic (or neural) control of blood pressure via feedback mechanisms. Changes in mean blood pressure are detected by baroreceptors, which relay information to the cardiovascular centers in the brainstem controlling PANS and SANS outflow. For example, an increase in mean blood pressure elicits baroreceptor discharge,... 

Baroreceptors increase their firing rate with increased blood pressure. Therefore, a decrease in baroreceptor sensitivity would decrease input to the vasomotor center, which would be interpreted by the vasomotor center as a decrease in blood pressure. This would lead to an increase in sympathetic outflow. The answer is (E). (If you chose a different answer, review the components of the autonomic and hormonal feedback loops for the maintenance of blood pressure Figure 6-4.)... 

---