Diuretics are among the most commonly used drugs. They primarily block active reabsorption of sodium at different sites in the nephron, thereby increasing urinary losses of NaCl and H2O. This ability to induce a negative fluid balance has made these drugs particularly useful in the treatment of a variety of conditions, edematous: congestive heart failure, nephrotic syndrome, liver cirrhosis, chronic renal failure, idiopathic edema, and nonedematous states: hypertension, hypercalcemia, nephrolithiasis, and syndrome of inappropriate antidiuretic hormone secretion. The diuretics are generally divided into three major classes, which are distinguished by the sites at which they impair the sodium reabsorption: loop diuretics at the thick ascending limb of the loop of Henle, thiazide-type diuretics at the distal tubule, and potassium-sparing diuretics at the cortical collecting tubule. The loop diuretics that are generally the most potent are furosemide, torasemide, and ethacrynic acid. The thiazide-type diuretics include chlorothiazide and metolazone. Spironolactone and amiloride are potassium-sparing diuretics. Diuretics should be started at an effective single dose and given intermittently with a subsequent increase in dose or frequency of administration. As a general rule, the rate of diuresis in an edematous patient should not exceed 1 to 2kg weight loss per day. In renal failure patients, loop diuretics at a higher than normal dose are required to get the desired diuretic effect because the diuretic excretion is often limited, in part due to the retention of organic anions. The patients with liver cirrhosis are responsive to spironolactone. After the administration of diuretics, even if a net diuresis is induced, the response is short-lived as a new steady state is rapidly established because the diuretic-induced sodium losses are counterbalanced by neuro-humorally mediated increases in tubular reabsorption at nondiuretic sensitive sites. This process is called compensatory antidiuresis or diuretic tolerance. Therefore sodium restriction is important when a patient is taking loop diuretics, and the concurrent use of a thiazide diuretic can inhibit downstream NaCl reabsorption, resulting in an exaggeration of diuresis. The most common side-effects are those encountered in virtually all the effective drugs: hypovolemia, hypokalemia and potassium depletion, hyperuricemia, and metabolic alkalosis. Other side-effects include hyperglycemia, hyperlipidemia, hyperuricemia, ototoxicity and sexual dysfunction. In addition, diuretics have the potential to increase the toxicity of several other agents. Nonsteroidal antiinflammatory drugs may antagonize the natriuretic effects of diuretics. The combination of potassium-sparing diuretics and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers may result in severe hyperkalemia.
Alkalosis ; Amiloride ; Angiotensin Receptor Antagonists ; Angiotensin-Converting Enzyme Inhibitors ; Anions ; Chlorothiazide ; Diuresis ; Diuretics* ; Edema ; Ethacrynic Acid ; Extremities ; Furosemide ; Heart Failure ; Humans ; Hypercalcemia ; Hyperglycemia ; Hyperkalemia ; Hyperlipidemias ; Hypertension ; Hyperuricemia ; Hypokalemia ; Hypovolemia ; Kidney Failure, Chronic ; Liver Cirrhosis ; Loop of Henle ; Metolazone ; Natriuretic Agents ; Nephrolithiasis ; Nephrons ; Nephrotic Syndrome ; Potassium ; Renal Insufficiency ; Sodium ; Sodium Potassium Chloride Symporter Inhibitors ; Spironolactone ; Water-Electrolyte Balance ; Weight Loss

Hyponatremia is a commonly observed complication that is related to hypoalbuminemia and portal hypertension in patients with advanced liver cirrhosis. Hyponatremia in patients with liver cirrhosis is mostly dilutional hyponatremia and is defined when the serum sodium concentration is below 130 meq/L. The risk of complications increases significantly in cirrhotic patients with hyponatremia, which includes spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy. In addition, hyponatremia is associated with increased morbidity and mortality in patients with cirrhosis, and is an important prognostic factor before and after liver transplantation. The conventional therapies of hyponatremia are albumin infusion, fluid restriction and loop diuretics, but these are frequently ineffective. This review investigates the pathophysiology and various therapeutic modalities, including selective vasopressin receptor antagonists, for the management of hyponatremia in patients with liver cirrhosis.
Antidiuretic Hormone Receptor Antagonists ; Fibrosis ; Hepatic Encephalopathy ; Hepatorenal Syndrome ; Humans ; Hypertension, Portal ; Hypoalbuminemia ; Hyponatremia* ; Liver Cirrhosis* ; Liver Transplantation ; Liver* ; Mortality ; Peritonitis ; Sodium ; Sodium Potassium Chloride Symporter Inhibitors

Diuretics are commonly used to control edema across various clinical fields. Diuretics inhibit sodium reabsorption in specific renal tubules, resulting in increased urinary sodium and water excretion. Loop diuretics are the most potent diuretics. In this article, we review five important aspects of loop diuretics, in particular furosemide, which must be considered when prescribing this medicine: (1) oral versus intravenous treatment, (2) dosage, (3) continuous versus bolus infusion, (4) application in chronic kidney disease patients, and (5) side effects. The bioavailability of furosemide differs between oral and intravenous therapy. Additionally, the threshold and ceiling doses of furosemide differ according to the particular clinical condition of the patient, for example in patients with severe edema or chronic kidney disease. To maximize the efficiency of furosemide, a clear understanding of how the mode of delivery will impact bioavailability and the required dosage is necessary.
Biological Availability ; Diuretics ; Edema ; Furosemide ; Humans ; Renal Insufficiency, Chronic ; Sodium ; Sodium Potassium Chloride Symporter Inhibitors*

Diuretic therapy for the treatment of edema in patients with end-stage renal disease (ESRD) is unsatisfactory, and a combination of thiazide and loop diuretics may produce better clinical effects. To evaluate the influence of thiazide on loop diuretic therapy for ESRD, we performed a crossover study of furosemide versus hydrochlorothiazide plus furosemide treatment. The diuretic effects of furosemide (160 mg i.v.) alone versus a combination of hydrochlorothiazide (100 mg p.o.) and furosemide were studied in ten ESRD patients with proteinuria greater than 1 g/day. The diuretic effects were compared for 24 h urine volume and electrolyte excretion. To detect the influence of thiazide that may have been obscured in the widely dispersed data, pharmacodynamic analysis of urine furosemide excretion rate versus fractional excretion of sodium (FeNa) was also performed using mixed-effect modeling. Combination therapy was not significantly different from furosemide monotherapy in terms of 24 h urine volume, chloride, or sodium excretion. Hydrochlorothiazide was not a significant covariate in the furosemide effect for the pharmacodynamic model. In patients with ESRD and severe proteinuria (>1,000 mg/day), the combination of hydrochlorothiazide with furosemide therapy did not increase the diuretic effect of furosemide.
Cross-Over Studies ; Diuretics ; Edema ; Furosemide ; Humans ; Hydrochlorothiazide* ; Kidney Failure, Chronic* ; Proteinuria ; Sodium ; Sodium Potassium Chloride Symporter Inhibitors

It has been known that central tryptaminergic system is closely related with the regulation of renal function, and that central 5-HT1 receptors mediate diuresis and natriuresis, whereas central 5-HT2 and 5-HT3 receptors mediate antidiuresis and antinatriuresis. Among many subtypes of 5-HT1 receptors, central 5-HT1A subtype has been suggested to exert diuretic and natriuretic effets. Further, it was recently observed that TFMPP, 5-HT1B agonist, elicited profound diuresis and natriuresis when administered intracerebroventricularly(icv). Present study is therefore undertaken to delineate the mechanism involved in the natriuresis and diuresis induced by icv TFMPP, employing the denervated and vagotomized rabbits. The influence of icv TFMPP on the plasma level of ANP was also observed. TFMPP 250 microgram/kg icv produced marked diuresis and natriuresis. Renal hemodynamics showed significant increase only in the first 10-min period after administration and thereafter tended to recover. However, natriuretic action lasted even after the increased renal hemodynamics returned to the control level, suggesting the decreased Na reabsorption in the tubules by humoral natriuretic factors. Systemic blood pressure transiently increased. In rabbits in which one kidney is denervated, with the contralateral intact as the control kidney, the denervated kidney also responded with natriuresis and diuresis like that of the normal rabbit. The contralateral kidney responded with typical diuretic and natriuretic effects, along with the marked increased of renal hemodynamics. The plasma ANP, one of humoral natriuretic factors, increased after administration of icv TFMPP, peaking at about 15min. In bilaterally vagotomized rabbits, the natriuretic and diuretic effects produced by icv TFMPP were greater than that of the normal rabbits. These observations suggest that the natriuresis and diuresis elicited by icv TFMPP result from the inhibition of tubular Na reabsorption mainly through mediation of ANP. It has been also suggested that vagus nerve might exert inhibitory influence on the diuretic action of icv TFMPP, because the renal effects was augmented in the vagotomized rabbits.
Atrial Natriuretic Factor ; Blood Pressure ; Diuresis ; Diuretics ; Hemodynamics ; Kidney ; Natriuresis ; Natriuretic Agents ; Negotiating ; Plasma ; Rabbits* ; Receptors, Serotonin, 5-HT1 ; Receptors, Serotonin, 5-HT3 ; Serotonin 5-HT1 Receptor Agonists ; Vagus Nerve

Acute decompensated heart failure syndrome is the most common cause of cardiovascular hospitalization with a high rate of in-hospital mortality. The clinical presentation is characterized by different clinical profiles due to various underlying causes, precipitating factors, volume status, and tissue perfusion status. Therefore, clinicians should carefully examine the hemodynamic status of acute decompensated heart failure patients in the initial management. Risk stratification might provide guidance to clinicians who care for patients with acute decompensated heart failure syndromes, and might improve decision-making in emergent care when decisions must be made quickly and accurately. Intravenous loop diuretics are the main treatment option for the relief of congestive symptoms. This article reviews how to assess hemodynamic status of acute decompensated heart failure patients and how to perform risk stratification of patients. Additionally, the initial treatment approach with a variety of pharmacological therapies including inotropic agents, diuretics, beta-blockers, angiotensinogen converting enzyme-inhibitors, angiotensin receptor blockers, digoxin, and other medications that are routinely prescribed in the management of acute decompensated heart failure patients are also discussed.
Angiotensin Receptor Antagonists ; Angiotensinogen ; Digoxin ; Diuretics ; Estrogens, Conjugated (USP) ; Heart Failure* ; Hemodynamics ; Hospital Mortality ; Hospitalization ; Humans ; Perfusion ; Precipitating Factors ; Sodium Potassium Chloride Symporter Inhibitors

BACKGROUND: Head-down suspension (HDS) of rats has been used as a model for simulation of a microgravity environment. C-type natriuretic peptides (CNP) and atrial natriuretic peptide (ANP) are produced in the central nervous system, especially in hypothalamus, to complement their peripheral natriuretic effects. Therefore, this study investigated the changes in the central adaptations of hypothalamic ANP and CNP syntheses to 4 weeks of HDS in rats. METHODS: Unanesthetized, unrestrained, male Sprague-Dawley rats were subjected to either a horizontal position (control rats) or a -45 degrees head-down tilt using the tail-traction technique (HDS rats). We determined the hypothalamic syntheses of natriuretic peptides as an expression of ANP and CNP mRNA. The expression of natriuretic peptide mRNA was measured by reverse transcription-polymerase chain reaction with [32P]-dCTP following 4 weeks of HDS in the hypothalamus of control and HDS rats. RESULTS: After 4 weeks of HDS, the expression of ANP mRNA showed a decreasing trend in the hypothalamus of HDS rats. In contrast with ANP, CNP mRNA expression was significantly (p<0.01) increased in the hypothalamus of HDS rats. There were different changes in the hypothalamic CNP and ANP mRNA expressions of HDS rats compared with that of the control rats.CONCLUSION: These results represent that the hypothalamic syntheses of natriuretic peptides are differently responded and the role of CNP is augmented to compensate for the decrement of ANP action in the central nervous system following 4 weeks of HDS.
Animals ; Atrial Natriuretic Factor ; Central Nervous System ; Complement System Proteins ; Head-Down Tilt ; Humans ; Hypothalamus ; Male ; Natriuretic Agents ; Natriuretic Peptides ; Rats* ; Rats, Sprague-Dawley ; RNA, Messenger* ; Weightlessness

Anxiety disorder is one of the most common mental disorders and seriously impairs the physical and mental health of patients. Due to the efficacy of acupuncture for tranquilization, acupuncture displays its unique advantage on the treatment of anxiety disorder, but the relevant biological mechanism has not been elaborated. The modern medicine study has proved that the heart and brain have their own independent natriuretic peptide (NP) system. The dysfunction of ANP and its receptor are closely related to the occurrence of anxiety disorder. The ANP acts on anti-anxiety. Hence, focusing on the three aspects, named the anti-anxiety effect of acupuncture based on its tranquilizing effect, the anti-anxiety effect of ANP and the positive regulation of acupuncture on NP, the mechanism on ANP and its receptor was explored in anti-anxiety with acupuncture based on tranquilizing effect, and the idea was put forward on that the anti-anxiety effect of acupuncture was possibly based on its action of tranquilization through regulating the ANP and its receptor. As a result, it is expected to provide the theoretic support for the mechanism study on anti-anxiety with acupuncture based on its tranquilizing effect.
Acupuncture Therapy ; Animals ; Anti-Anxiety Agents ; metabolism ; Anxiety ; metabolism ; therapy ; Atrial Natriuretic Factor ; metabolism ; Humans ; Receptors, Atrial Natriuretic Factor ; metabolism

Heart Failure ; Humans ; Sodium Potassium Chloride Symporter Inhibitors

The renal function is under regulatory influence of central nervous system, in which various neurotransmitter and neuromodulator systems take part, and it has been known that kallikrein-kininogen- kinin system exists also in the brain, but its physiological role remains to be explored. This study was, therefore, undertaken to delineate the possible role of central kinin system in the regulation of renal function. Kallikrein given into a lateral ventricle(icv) of rabbit brain in doses ranging from 3 to 30 microgram/kg icv elicited increases in Na excretion and the fraction of filtered sodium excreted(FENa), as well as in urine flow rate. K excretion, however, did not parallel the Na excretion, but tended to decrease when the natriuresis reached its peak. Renal blood flow and glomerular filtration did not significantly change. Neither did free water reabsorption significantly change, but tended to decrease. The systemic blood pressure slightly increased. When 30 microgram/kg kallikrein was given intravenously, all the parameters of renal function and systemic blood pressure did not show any increase but decrease, primarily by decreased renal hemodynamics, resulting from transient hypotension. In experiments in which the plasma ANP was measured, the ANP level markedly increased, reaching more than 5 times the control value 25min after 30 microgram/kg icv, and lasting until the end of the experiment at 80min. The renal nerve activity increased with kallikrein, 30 microgram/kg icv, peaking at 1 min but it remained slightly increased until about 40 min, and then slightly declined. This indicates that the increased renal nerve activity may have antagonized or ameliorated the natriuretic effect of icv kallikrein. Lys-bradykinin(kallidin), a cleavage product from kallidinogen by kallikrein, when given icv in doses of 0.3 to 30 microgram/kg also produced increased Na excretion and diuresis. When CHA, a kallikrein inhibitor, was given icv in doses of 3-30 microgram/kg, elicited antidiuresis and antinatriuresis. However, pretreatment with CHA tended slightly to suppress the kallikrein effect. These results indicate that the central kallikrein- kinin system is involved in the central regulation of renal function, the activation of the system in the CNS resulting in increased natriuresis and diuresis, which are related to increased plasma ANP level, with the possible antagonistic effects of increased renal nerve activity.
Atrial Natriuretic Factor ; Blood Pressure ; Brain ; Central Nervous System ; Diuresis ; Filtration ; Hemodynamics ; Hypotension ; Kallidin* ; Kallikreins* ; Natriuresis ; Natriuretic Agents ; Neurotransmitter Agents ; Plasma ; Renal Circulation ; Sodium ; Water