Neurohumoral mechanisms

Tolins JP, Raij L. Adverse effect of amphotericin B administration on renal hemodynamics in the rat. Neurohumoral mechanisms and influence of calcium channel blockade. J Pharmacol ExpTher 1988 245 594-9. 

Under normal circumstances, these quantities are well within the range of the total absorptive capacity of the small bowel ( 16 L) and colon (4-5 L). Neurohumoral mechanisms, pathogens, and drugs can alter these processes, resulting in changes in either secretion or absorption of fluid by the intestinal epithelium. Altered motility also contributes to this process, as the extent of absorption parallels transit time. With decreased motility and excess fluid removal, feces can become inspissated and impacted, leading to constipation. When the capacity of the colon to absorb fluid is exceeded, diarrhea will occur. 

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... 

Packer M (1992) The neurohumoral hypothesis a theory to explain the mechanism of disease progression in heart failure. J Am Coll Cardiol 20 248-254 Pepperl DJ, Regan JW (1993) Selective coupling of a2-adrenergic receptor subtypes to cAMP-dependent reporter gene expression in transiendy transfected JEG-3 cells. Mol Pharmacol 44 802-809... 

Neurohumoral (extrinsic) compensation involves two major mechanisms (previously presented in Figure 6-7)—the sympathetic nervous system and the renin-angiotensin-aldosterone hormonal response—plus several others. Some of the pathologic as well as beneficial features of these compensatory responses are illustrated in Figure 13-2. The baroreceptor reflex appears to be reset, with a lower sensitivity to arterial pressure, in patients with heart failure. As a result, baroreceptor sensory input to the vasomotor center is reduced even at normal pressures sympathetic outflow is increased, and parasympathetic outflow is decreased. Increased sympathetic outflow causes tachycardia, increased cardiac contractility, and increased vascular tone. Vascular tone is further increased by angiotensin II and endothelin, a potent vasoconstrictor released by vascular endothelial cells. The result is a vicious cycle that is characteristic of heart failure (Figure 13-3). Vasoconstriction increases afterload, which further reduces ejection fraction and cardiac output. Neurohumoral antagonists and vasodilators... 

The advantages of the isolated vessel technique in defining microvascular physiologic and pathophysiologic mechanisms are 1) The vessels are studied in the absence of a neurohumoral and parenchymal tissue environment, 2) it allows for direct assessment of vascular responses in defined segments, 3) transmural pressure is controlled, 4) hormones and drugs can be added to the bathing media or luminal perfusate, 5) intracellular ion concentrations can be measured by fluorescence microscopy and membrane potentials can be recorded with microelectrodes. 

Future directions may include modifying neurohumoral activation, inhibiting endothelin, and altering intracellular mechanisms and extracellular matrix structures. 

The number of known specific peptides that serve neuromodulator neurotransmitter or neurohumoral roles is expanding at a rapid rate, and a discussion of all the individual peptides is beyond the scope of this article. The detailed mechanisms controlling the synthesis of these peptides are not well understood, although general concepts concerning peptide synthesis are now emerging. The reader is referred to a recent volume (Krieger et al., 1983). 

Hall JE, do Carmo JM, Da Silva AA, Wang Z, Hall ME (2015) Obesity-induced hypertension interaction of neurohumoral and renal mechanisms. Cite Res 116 991-1006 Harvey A, Montezano AC, Touyz RM (2015) Vascular biology of ageing impUcations in hypertension. J Mol Cell Cardiol 83 112-121... 

Acetylcholine, supposedly a neurohumoral transmitter, is a compound effective in amounts of the same order of magnitude as vitamins or hormones. It was to be expected that the study of the enzyme mechanisms connected with this ester, as well as other enzymes involved in nerve activity, should yield much information. In this way the electrical changes during the activity could eventually be correlated with chemical reactions. 

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