Kidneys sympathetic nervous system effects

Although blood pressure control follows Ohm s law and seems to be simple, it underlies a complex circuit of interrelated systems. Hence, numerous physiologic systems that have pleiotropic effects and interact in complex fashion have been found to modulate blood pressure. Because of their number and complexity it is beyond the scope of the current account to cover all mechanisms and feedback circuits involved in blood pressure control. Rather, an overview of the clinically most relevant ones is presented. These systems include the heart, the blood vessels, the extracellular volume, the kidneys, the nervous system, a variety of humoral factors, and molecular events at the cellular level. They are intertwined to maintain adequate tissue perfusion and nutrition. Normal blood pressure control can be related to cardiac output and the total peripheral resistance. The stroke volume and the heart rate determine cardiac output. Each cycle of cardiac contraction propels a bolus of about 70 ml blood into the systemic arterial system. As one example of the interaction of these multiple systems, the stroke volume is dependent in part on intravascular volume regulated by the kidneys as well as on myocardial contractility. The latter is, in turn, a complex function involving sympathetic and parasympathetic control of heart rate intrinsic activity of the cardiac conduction system complex membrane transport and cellular events requiring influx of calcium, which lead to myocardial fibre shortening and relaxation and affects the humoral substances (e.g., catecholamines) in stimulation heart rate and myocardial fibre tension. 

This is the presence of excess fluid in the peritoneal cavity, leading to a swollen abdomen (Figure 4.3). The accumulation of ascitic fluid represents a state of sodimn excess in the body. Patients often present with hyponatraemia, but this is thought to be due to the dilutional effect of excess water rather than to low sodium. There are three theories of the cause of ascites formation. The underfill theory suggests that there is a reduction in circulating plasma volume as a result of accumulation in the splanchnic area due to vascular dilatation in portal hypertension. This activates the plasma renin, aldosterone and sympathetic nervous systems, which leads to sodium and water retention by the kidneys. 

BZ is a competitive inhibitor of muscarinic receptors associated with the parasympathetic nervous system that innervate the eyes, heart, respiratory system, skin, gastrointestinal tract, and bladder. The sweat glands, innervated by the sympathetic nervous system, are also modulated by muscarinic receptors. By any route of exposure, the onset of action is approximately 1 h, with peak effects occurring 8h postexposure. Signs and symptoms gradually subside over 2-4 days. Most of the absorbed BZ is excreted via the kidney. 

Corticosteroids, CSA, TAC, and impaired kidney graft function may cause post-transplant hypertension. The primary mechanism of CI-associated hypertension in heart transplant recipients may be related to the Cl-induced stimulation of intact renal sympathetic nerves and the absence of reflex cardiac inhibition of the sympathetic nervous system, but a number of other mechanisms, including decreased prostacyclin and nitric oxide production, also have been proposed. " In addition to the propensity to cause peripheral vasoconstriction, CIs promote sodium retention, resulting in extracellular fluid volume expansion. TAC appears to have less potential to induce hypertension following transplantation than CSA. Most classes of antihypertensive medications effectively reduce blood pressure in transplant patients (see Chap. 13). ... 

The naturally occurring catecholamines dopamine (1), norepinephrine (2), and epinephrine(3) (Figure 1) play key roles in neurotransmission, metabolism, and in the control of various physiological processes. For example, norepinephrine is the primary neurotransmitter in the sympathetic nervous system and also functions as a neurotransmitter in the central nervous system. Epinephrine, elaborated by the adrenal gland, has potent effects on the heart, vascular and other smooth muscles. Dopamine is an important neurotransmitter in the central nervous system, and has important peripheral effects in such organs as the kidney and heart. The importance of these effects has made the search for drugs that can mimic, inhibit, or otherwise modulate the effects of these catecholamines an important area of medicinal chemistry. 

The first successful drug treatments for hypertension were introduced after World War II. By that time, researchers had learnt that blocking the sympathetic nervous system could lower blood pressure. In 1946, tetraethyl-ammonium, a drug known for 30 years to block nerve impulses, was introduced as a treatment for hypertension. Hexamethonium, an improved version of tetraethylammo-nium, was available for use by 1951. Another effective blood pressure-lowering drug, hydralazine, resulting from the search for antimalarial compounds, was diverted to the treatment of hypertension when it was found to have no antimalarial activity, but to lower blood pressure and increase kidney blood flow. 

The chromaffin cells of the adrenal medulla may be considered to be modified sympathetic neurons that are able to synthesize E from NE by /V-methylation. In this case the amine is Hberated into the circulation, where it exerts effects similar to those of NE in addition, E exhibits effects different from those of NE, such as relaxation of lung muscle (hence its use in asthma). Small amounts of E are also found in the central nervous system, particularly in the brain stem where it may be involved in blood pressure regulation. DA, the precursor of NE, has biological activity in peripheral tissues such as the kidney, and serves as a neurotransmitter in several important pathways in the brain (1,2). 

The kidney brush border also possesses a carnosine transport system and there is evidence that kidney also contains an active carnosinase (Sauerhoefer et al., 2005). There is also evidence that carnosine can influence sympathetic nervous activity in kidney (Tanida et al., 2005) as well as brown (Tanida et al., 2007) and white adipose tissue (Shen et al., 2008). Other studies have shown that carnosine has antidepressant activity in rats (Tomonaga et al., 2008). In chicks, carnosine induces hyperactivity (Tsuneyoshi et al., 2007) whereas its reverse structure (L-histidinyl-13-alanine) has sedative and hypnotic effects (Tsuneyoshi et al., 2008). The mechanisms involved in remain obscure however. 

Adrenoceptors of the /3-subtype are important mediators of the sympathetic activation of the heart, kidney, and bronchi. /3-Adrenoceptors are also found in other organs and tissues such as blood vessels and the central nervous system. Accordingly, /3-adrenoceptor antagonists or jS-blockers inhibit the stimulating influence of the endogenous catecholamines (noradrenaline, adrenaline) on the various organs and tissues which are subject to sympathetic innervation. In cardiovascular medicine the /3-blockers are used in particular to blunt the sympathetic activation of the heart and kidneys. These effects are mediated by the /3i-subtype of the /3-adrenoceptors. The currently used /3-blockers are all competitive antagonists of the /3i-adrenoceptor, which is the basis of their therapeutic application. 

In animals, AM dilates resistance vessels in the kidney, brain, lung, hind limbs, and mesentery, resulting in a marked, long-lasting hypotension. The hypotension in turn causes reflex increases in heart rate and cardiac output. These responses also occur during intravenous infusion of the peptide in healthy human subjects. AM also acts on the kidneys to increase sodium excretion, and it exerts several endocrine effects including inhibition of aldosterone and insulin secretion. It acts on the central nervous system to increase sympathetic outflow. 

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