Low-pressure receptors

Figure 15.4 Effects of the autonomic nervous system on mean arterial pressure. The baroreceptors, chemoreceptors, and low-pressure receptors provide neural input to the vasomotor center in the brainstem. The vasomotor center integrates this input and determines the degree of discharge by the sympathetic and parasympathetic nervous systems to the cardiovascular system. Cardiac output and total peripheral resistance are adjusted so as to maintain mean arterial pressure within the normal range.

Low-pressure receptors. The low-pressure receptors are located in the walls of the atria and the pulmonary arteries. Similar to baroreceptors, low-pressure receptors are also stretch receptors however, stimulation of these receptors is caused by changes in blood volume in these low-pressure areas. An overall increase in blood volume results in an increase in venous return an increase in the blood volume in the atria and the pulmonary arteries and stimulation of the low-pressure receptors. These receptors then elicit reflexes by way of the vasomotor center that parallel those of baroreceptors. Because an increase in blood volume will initially increase MAP, sympathetic discharge decreases and parasympathetic discharge increases so that MAP decreases toward its normal value. The simultaneous activity of baroreceptors and low-pressure receptors makes the total reflex system more effective in the control of MAP. 

A more moderate stimulus for thirst and ADH secretion is a decrease in extracellular fluid, or plasma volume. This stimulus involves low-pressure receptors in the atria of the heart as well as baroreceptors in the large arteries. A decrease in plasma volume leads to a decrease in atrial filling, which is detected by low-pressure receptors, and a decrease in MAP, which the baroreceptors detect. Each of these receptors then provides excitatory inputs to the thirst center and to the ADH-secreting cells. 

This fall in both arterial pressure and cardiac filling leads to the activation of two different groups of pressure receptors, consisting of the high-pressure receptors of the carotid sinus and aortic arch and the low-pressure receptors of the heart and lungs (2). Within the heart there are mechanoreceptors linked by unmyelinated vagal afferents in all four cardiac chambers. These mechanoreceptors produce a tonic inhibitory effect on the cardiovascular control centers of the medulla. 

The regulation of the total peripheral resistance also involves the complex interactions of several mechanisms. These include baroreflexes and sympathetic nervous system activity response to neurohumoral substances and endothelial factors myogenic adjustments at the cellular level, some mediated by ion channels and events at the cellular membrane and intercellular events mediated by receptors and mechanisms for signal transduction. As examples of some of these mechanisms, there are two major neural reflex arcs (Fig. 1). Baroreflexes are derived from high-pressure barorecep-tors in the aortic arch and carotid sinus and low-pressure cardiopulmonary baroreceptors in ventricles and atria. These receptors respond to stretch (high pressure) or... 

Thrasher TN. Baroreceptor regulation of vasopressin in renin secretion Low pressure vs. high pressure receptors (Review). Front Neuroendocrinol 1994 15 157-96. 

The bladder functions as a low-pressure reservoir, filling at the rate of 2 mL/min until approximately 360-400 mL is reached, and the intravesical pressure increases. This pressure activates proprioceptive receptors in the bladder wall to signal the sacral spinal cord, thus triggering detrusor contraction. Sensory stimulation occurs at the micturation center in the brainstem that coordinates urethral sphincter relaxation as the detrusor muscle contracts. Higher controls in the frontal lobe can block this sensory message until conscious direction permits a voluntary void. Medical insults to the spinal column, peripheral sensory nerves, and cerebral cortex will cause malfunction in the voiding pattern (7). 

Apart from possible clinical differences between the P-block-ers approved for HF, selection of a p-blocker may also be affected by pharmacologic differences. Carvedilol exhibits a more pronounced blood pressure lowering effect and thus causes more frequent dizziness and hypotension as a consequence of its ar receptor blocking activity. Therefore, in patients predisposed to symptomatic hypotension, such as those with advanced LV dysfunction (LVEF less than 20%) who normally exhibit low systolic blood pressures, metoprolol succinate may be the most desirable first-line P-blocker. In patients with uncontrolled hypertension, carvedilol may provide additional antihypertensive efficacy. 

Low-dose dopamine is not without adverse reactions and most studies have failed to evaluate its potential toxicities. Adverse reactions that may be associated with low-dose dopamine include tachycardia, arrhythmias, myocardial ischemia, depressed respiratory drive, and gut ischemia. Low-dose dopamine has also been postulated to impair resistance to infection through a reduction in prolactin concentrations.21 Furthermore, significant overlap in receptor activation occurs. Therefore, doses considered to activate only dopamine receptors may increase cardiac output and blood pressure through dopamine s effect on 3- or a-adrenergic receptors. 

V. cholerae is a gram-negative bacillus. Vibrios pass through the stomach to colonize the upper small intestine. Vibrios have filamentous protein extensions that attach to receptors on the intestinal mucosa, and their motility assists with penetration of the mucus layer.2 The cholera enterotoxin consists of two subunits, one of which (subunit A) is transported into the cells and causes an increase in cyclic AMP, which leads to a deluge of fluid into the small intestine.20 This large volume of fluid results in the watery diarrhea that is characteristic of cholera. The stools are an electrolyte-rich isotonic fluid, the loss of which results in blood volume depletion followed by low blood pressure and shock.2 Of note, the diarrheal fluid is highly infectious. 

Dopamine is found in every sympathetic neuron and ganglion in the CNS. As a drug, and in addition to stimulation of dopaminergic receptors, dopamine indirectly stimulates both a- and )3-adrenoreceptors. Dopamine also causes a release of endogenous norepinephrine. The mechanism of action is based on the excitatory effect on )3-adrenoreceptors (in low and moderate doses), as well as on a-adrenoreceptors (in large doses). It has a positive inotropic effect on the heart, increases blood supply, selectively widens renal and mesenteric blood vessels, does not elevate blood pressure, and slightly increases the frequency of heartbeats. 

The glomerulus is situated between two sets of resistance vessels, the afferent and efferent arterioles, thus preventing transmission of this pressure to the glomerulus. This compensatory mechanism may be one explanation for the relatively low incidence of hypertensive nephrosclerosis (1.5-4%) among patients with mile to moderate hypertension. In the intrarenal vasculature, angiotensin receptors are found in greater density in the efferent... 

These compounds include NE, which acts on both a and P receptors, and epinephrine, which is more active on p receptors. As mentioned previously, catecholamines lacking a 4-OH group, such as phenylephrine (4.47) and methoxamine (4.48), show almost pure a, activity. They are both vasoconstrictors, used in treating hypotension (low blood pressure) and nasal congestion. These drugs may also inhibit insulin release. 

Butorphanol tartrate is a weak partial p-receptor agonist, 3.5-5 times as potent as morphine. The incidence of psychotomimetic effects is relatively low. The recommended doses are 1-4 mg intramuscularly every 3-4 h or 0.5-2 mg intravenously. Respiratory depression produced by butorphanol 2 mg IV is similar to that of 10 mg morphine. However, there is a ceiling effect for respiratory depression, and near-maximum depression occurs after 4 mg in normal adults. In healthy volunteers, butorphanol 0.03-0.06 mg-kg-1 produces no significant cardiovascular changes. However, in patients with cardiac disease, progressive increases in cardiac index and pulmonary artery pressure occur, and butorphanol should be avoided in patients with recent myocardial infarction. Butorphanol is metabolised mainly in the liver to inactive metabolites. The terminal half-life is 2.5-3.5 h. 

Prazosin, doxazosin, and terazosin are all efficacious in patients with BPH. These drugs are particularly useful in patients who also have hypertension. Considerable interest has focused on which -receptor subtype is most important for smooth muscle contraction in the prostate subtype-selective K1A-receptor antagonists might lead to improved efficacy and safety in treating this disease. As indicated above, tamsulosin is also efficacious in BPH and has relatively minor effects on blood pressure at a low dose. This drug may be preferred in patients who have experienced orthostatic hypotension with other -receptor... 

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