Digitalis

The most important contribution of herbal medicine to the materia medica of the 18th century was foxglove. The purple foxglove, a rather common plant growing throughout the greater part of Europe, is not mentioned by the founding father of herbal medicine, Dioscorides, or in any of the ancient herbals. In the Middle Ages, Welsh physicians employed the foxglove for the preparation of external remedies. It was then known as foxes-glew or foxes-music, because of its resemblance to an ancient...

Cardiovascular Capacitance

Relationships between sodium balance and arterial pressure. such as enhanced production of endogenous vasodilator substances and adaptation of baroreflex activity have also been suggested to contribute to the reduced arterial pressure. In uncomplicated essential hypertensive subjects, effective antihypertensive action is usually associated with a sustained moderate reduction of extracellular fluid and plasma volumes. Thus, the correction of arterial pressure and effective blood volume...

The Overflow Hypothesis

The underfill hypothesis has been challenged on several fronts. Lieberman, Levy, their co-workers, and others have advanced clinical and experimental data which challenge the early sequence shown in Fig. 1 15,16 . Careful studies of dogs with experimental cirrhosis and patients with early hepatic cirrhosis demonstrate that renal salt and water retention can develop prior to the formation of ascites or edema. The classic underfill hypothesis requires that ascites and or edema develop first, to...

Atrial Natriuretic Peptide and Related Peptides

The original peptide (see Fig. 4) was discovered by purification of atrial extracts which exhibited striking diuretic and natriuretic properties 6, 58 . Atrial natriuretic peptide is stored in secretory granules of the atrial myocyte as a 126-amino-acid propeptide (pro-ANP) which is cleaved during or soon after secre- FIGURE 4. Structure of human atrial natriuretic peptide (human ANP) and urodilatin (Human URO). Darkened amino acid residues on human URO represent an amino terminal extension...

Calcium Activation Mechanisms

Renal blood flow and intrarenal capillary dynamics are regulated by a variety of mechanisms that control vascular smooth muscle and mesangial cell contractile activity. As with other vascular smooth muscle cells, contraction of renal vascular cells is elicited primarily by increases in intracellular Ca2+ activity. Although extracellular fluid Ca2+ is in the millimolar range, cytosolic Ca2+ is maintained at considerably lower levels, (about 10 7 M) through active extrusion of Ca2+ from the cell...

Insulin Resistance

As already mentioned the insulin-resistant state associated with hypertension may be aggravated by therapy with potassium wasting diuretics. In this regard, several authors have suggested that the responses are in part explained by insulin resistance. Increased plasma insulin levels can increase hepatic VLDL production, thereby giving rise to both hypertriglyceridemia as well as increased LDL via intravascular catabolism of VLDL by lipoprotein lipase which is stimulated by insulin. Further,...

Prevention and Treatment of Diuretic Induced Hypokalemia

The first approach to preventing diuretic-induced hypokalemia is to use the lowest dose possible (Table 1). With regard to thiazide diuretics, the majority of the blood pressure lowering effect is seen at doses of 12.5-25 mg day. At higher doses, further blood pressure lowering is minimal, but rather, metabolic side-effects such as hypokalemia, hyperglycemia, and hypercholesterolemia become more prevalent. Dietary manipulations can also be utilized in the prevention and treatment of...

Potassium Sparing Diuretics

These diuretics are the sodium channel blockers amiloride and triamterene and the antialdosterone spironolactone. They all have weak natriuretic effects and are antikaliuretic (see Fig. 6). Spironolactone is specifically indicated in hypertension due to primary mineralocorticoid excess, although in adrenal hyperplasia and hyperaldosteronism amiloride may prove more effective in maintaining plasma potassium and controlling BP. The main problem with spironolactone is that doses above 100 mg daily...

Insulin Resistance Introduction

Thiazide diuretics remain the cornerstone of antihypertensive therapy and have been shown to reduce morbidity and mortality in hypertensive populations throughout the world. However, their use has been associated with a high incidence of endocrine disturbances including glucose intolerance. Glucose intolerance induced by thiazide diuretics was first reported in the late 1950s. Since then a variety of thiazides as well as loop diuretics have been reported to cause mild glucose intolerance, overt...

Mechanism of Hypokalemia Induced Glucose Intolerance

The precise molecular mechanism of hypokalemia-induced glucose intolerance is not completely understood however, the bulk of clinical and experimental evidence indicates that glucose-mediated beta cell insulin release plays a major role. Studies in normal volunteers have shown that thiazide-induced potassium deficiency sufficient to produce sustained hypokalemia is associated with decreased glucose utilization and subnormal plasma insulin response to hyperglycemia of 125 mg dl (hyperglycemic...

Renal Generation of Metabolic Alkalosis

Bicarbonate may be generated from renal or extrarenal sources (Table 1). The renal generation of bicarbonate involves, in general, three features (1) relatively high distal delivery of sodium salts (2) persistent mineralocorticoid exTABLE 1 Generation of Metabolic Alkalosis I. Excessive loss of acid Extrarenal Loss of acid into gastric juice vomiting, nasogastric suction Intestinal acid loss villous adenoma, congenital chloridorrhea Translocation of acid into cells K deficiency Renal Coupling...

Renal Salt and Water Retention [7

The presence of clinically apparent generalized edema represents the translocation of a large volume of fluid from the vascular to the interstitial space. If this occurs acutely, circulatory shock may result. This can occur when an acute increase in capillary permeability is produced by an allergic reaction or extensive burn. More commonly, edema develops relatively gradually and intravascular volume is maintained by avid renal salt and water retention. Consequently, in addition to the local...

The Use of Diuretics in the Treatment of Ascites and Edema in Hepatic Cirrhosis

Seldin* Department oj Internal Medicine, Baylor University Medical Center, Dallas, Texas 75246 and *University oj Texas Health Sciences Center, Dallas, Texas 75235 Cirrhosis of the liver is a major cause of salt and water retention. The tendency for accumulating fluid to localize in the peritoneal cavity is typical of cirrhosis and is far more pronounced than in congestive heart failure or the nephrotic syndrome. Although peripheral edema does occur with cirrhosis,...

Thiazidesensitive cotransporter mRNA

Effects of continuous loop diuretic infusion on rat kidney. Loop diuretic infusion increased the number of thiazide-sensitive Na Cl cotransporters (data from J. Am. Soc. Nephrol. 1 91 -98, 1990), the rate of thiazide-sensitive Na transport along the distal tubule (data from J. Clin. Invest. 83 113-126, 1989), the abundance of thiazide-sensitive Na-Cl cotransporter mRNA (A, furosemide-treated kidney cortex B, control kidney cortex Obermuller et al. Am. J. Physiol. 269 F900-F910, 1995,...

Pathophysiology Of Salt Retention And Edema The Underfill Vs Overflow Hypotheses

The accumulation of clinically significant systemic edema generally requires that the kidneys retain salt and water (the acute capillary leak syndromes are exceptions). Renal salt retention certainly develops in patients with nephrotic syndrome. The most proximal signal, or signals, responsible for the renal salt retention of these patients remain uncertain. The classic pathophysiologic explanation for the salt retention of nephrotic syndrome is the underfill hypothesis and follows the sequence...

Xanthines

Xanthine derivatives such as theophylline (see Fig. 9) have multiple actions on cells, including blockade of uptake of calcium into sarcoplasmic reticulum, inhibition of degradation of cyclic AMP and cyclic GMP by phosphodiesterase, and blockade of adenosine receptors 42 . The effects on calcium transport and cyclic nucleotide degradation occur at methylxanthine concentrations in the range of 0.5-1 mM, far above the therapeutic range of 20-50 fiM. By contrast, blockade of adenosine receptors...

Significance of Competition for Diuretic Secretion

Competitive inhibition between diuretics and other substances transported by the basolateral anion transporter has a number of clinical ramifications. Probenecid, the prototypic competitive inhibitor of basolateral anion transport, has been used by many investigators to determine the mode of entry of diuretics into the renal tubule lumen. Probenecid has been found to decrease the intensity of the natriuretic activity of chlorothiazide, hydrochlorothiazide, furose-mide, and piretanide,...

Volume Depletion and Increased Catecholamines

Volume depletion may reduce both renal blood flow and glomerular filtration rate, thereby reducing the filtered load of glucose and promoting hyperglycemia. In addition, it has been postulated that reduction in blood pressure and flow to muscle, the primary site of insulin-mediated glucose uptake, may be attributed to volume depletion. Thus volume depletion could reduce tissue sensitivity to insulin indirectly by limiting delivery to muscle bed. Increased plasma catecholamine levels...

Tubuloglomerular Feedback Mechanism

In addition to its role in mediating renal autoregulation, the TGF mechanism contributes significantly to the regulation of GFR and ultimately to the long-term control of sodium balance and extracellular fluid volume 4, 5, 38,39 . By operating in concert with glomerulotubular balance, the TGF mechanism stabilizes delivery of volume and solute to the distal nephron. As depicted in Fig. 3, flow-related changes in the tubular fluid composition at the macula densa are sensed and signals are...

Nonthiazide Hypocalciuric Diuretics

In addition to the thiazides, certain nonthiazide diuretics such as amiloride or indapamide have been shown to have hypocalciuric effects. These agents may also be of use in the management of idiopathic hypercalciuria or hypoparathyroidism. Amiloride, an antikaliuretic diuretic agent, is a pyrazine-carbonyl-guanidine that is unrelated chemically to other known antikaliuretic or diuretic agents. Compared to thiazide, it is a weak diuretic agent. Amiloride is not an aldosterone antagonist and its...

History of Diuretics

Department of Medicine, Baylor College of Medicine, Houston, Texas 77030 Diuretics, as therapeutic agents that act on the kidney to increase salt and water excretion, have a relatively short history. On the other hand, the very reason for which diuretics were developed, i.e., mobilization of excess body fluids, has a long history which dates back to the beginnings of medicine. No history of diuretics would be complete without some consideration of this long prelude, which is particularly...

ADH Antagonists

Since the synthesis of ADH (shown in Fig. 3) by Du Vigneaud and colleagues 19 , innumerable modifications of the peptide structure have been attempted, in order to develop specific antagonists to the different ADH receptor subtypes 31 . There are three receptor subtypes, all of which are membranes of the 7 membrane spanning G-protein-linked receptor family. V1A receptors are present in vascular and hepatic tissues, where they mediate vasoconstriction and glycogenolysis. V1B receptors, located...

Pharmacokinetics and Pharmacodynamics

Table 2 summarizes pharmacokinetic data in healthy subjects for the most commonly used loop diuretics. These drugs are absorbed quickly with peak serum concentrations attained within 0.5-2 hr. Furosemide exhibits what are called absorption-limited kinetics wherein its rate of absorption is slower than the rate of elimination. This feature manifests clinically as a delay in the peak time at which furosemide appears in blood or urine. In turn, the onset of effect of furosemide after oral dosing...

Use of Diuretics for the Treatment of Heart Failure

Sei.din* Department of Internal Medicine, Baylor University Medical Center, Dallas, Texas 75246 and *University of Texas Health Sciences Center, Dallas, Texas 75235 The congestive states are those disorders which create steady-state expansion of blood and extracellular fluid volume. They include congestive heart failure due to primary and secondary cardiac disorders of multiple etiologies. Heart failure may be defined as an inability of the heart, at normal filling...

Spironolactone Induced Gynecomastia

The pathophysiology of gynecomastia after spironolactone administration has been carefully studied in man. As noted above, spironolactone induces gynecomastia (and other antiandrogenic effects) principally by binding to cytosolic r SPIRONOLACTONE RECEPTOR COMPLEX FIGURE 2. Active androgens and more specifically 5a-dihydrotestosterone (DHT) interact with the androgen receptor (R) in target tissues to form hormone receptor complexes which activate protein synthesis. Low (50-75 mg) or high...

Ca2 Channel Antagonists and Other Direct Vasodilators

The natriuresis caused by agents that directly increase GFR may be due largely to their hemodynamic effects. Calcium channel blockers or antagonists refer to a large class of drugs that directly interfere with entry of Ca2+ via voltage-dependent calcium channels. Thus, calcium channel blockers will directly vasodilate preglomerular arterioles, leading to increases in RBF and GFR and will also block vasoconstrictor responses to agents that activate L-type voltage-dependent Ca2+ channels. As...

Acid Diuresis

Loop diuretics may increase distal tubular urinary hydrogen ion secretion and thus contribute to urinary acidification. Administration of arginine and lysine hydrochloride intravenously has also been used to achieve urinary acidification, but these agents can generate severe hyperkalemia and are therefore no longer used. Phencyclidine (PCP) is a weak base with a pKa value of 8.5, which is 90 metabolized and 10 secreted into the urine unchanged. Between 52 and 77 of the drug in blood is...

Classification Of Glaucoma

Glaucoma is not a single disorder, but rather multiple disorders (Table 1). There are multiple classification schemes. Glaucoma can be classified into congenital glaucoma, primary glaucoma, and secondary glaucoma. Congenital glaucoma is caused by an abnormality in the aqueous humor outflow tract in the anterior chamber. There may be other associated developmental ocular abnormalities. Primary glaucoma is divided into two categories, primary open angle glaucoma, and primary closed angle...

Antiandrogenic Effects

Caminos-Torres, R., Ma, L., and Snyder, R J. Gynecomastia and semen abnormalities induced by spironolactone in normal men. J. Clin. Endocrinol. Metab. 45, 255. 2. Dorfman, R. I. (1970). Biological activity of antiandrogens. Br. J. Derm. 82 (Suppl. 6), 3-8. 3. Dupont, A. (1985). Disappearance of spironolactone-induced gynecomastia during treatment with potassium canrenoate. The Lancet September, 731. 4. Juenemaitre, X., Chatellier, G., Kreft-Jais, C. et al. (1987). Efficacy and tolerance of...

Diuretics

When dietary salt restriction with, or without, additional bed rest does not adequately control edema, diuretic therapy is initiated. However, it must be emphasized that moderate dietary salt restriction continues to be an important component of therapy after diuretics are begun. The ingestion of a high salt diet together with diuretics will reduce their efficacy and increase the severity of adverse effects. The duration of action of many potent diuretics is relatively short. Daily or twice a...

Pathogenesis Of Ams [1114

It is highly likely that the pulmonary, peripheral, and cerebral forms of high altitude sickness share similar pathogenic mechanisms of impaired acclimatization (Fig. 1). Patients susceptible to AMS tend to demonstrate less weight loss than normal, do not diurese adequately and may actually gain weight they Hypoxia + Delayed Ventilatory Acclimatization Hypoxia + Delayed Ventilatory Acclimatization FIGURE 1. Pathogenesis of AMS. PAP, pulmonary artery pressure PVP, pulmonary venous pressure ANF,...

Hyperuricemia

M., Finch, R., and Lant, A. F. (1980). Studies on the mechanisms and characteristics of action of a uricosuric diuretic, indacrinone. Br. J. Clin. Pharmacol. 10, 249258. 2. Kahn, A. M. (1988). Effect of diuretics on the renal handling of urate. Semin. Nephrol. 8, 305314. 3. Langford, H. G., Blaufox, D., Borhani, N. O. et al. (1987). Is thiazide-produced uric acid elevation harmful Arch. Intern. Med. 147, 645-649. 4. Levy, D., Wilson, P. W. F., Anderson, K. M., and...

Renal Function In Heart Failure

About 20 of the cardiac output is normally delivered to the kidneys and virtually all of the renal blood flow (> 98 ) passes first through the glomeruli. Hydrostatic pressures within glomerular capillaries are regulated by constriction, or dilation, of preglomerular afferent arterioles and postglomerular efferent arterioles and by contraction or relaxation of periglomerular capillary mesangial cells. The hydrostatic pressures, surface area, and epithelial hydraulic permeability of glomerular...

Intensive Diuretic Therapy High Doses Combinations and Constant Infusions

West Haven VA Center for the Study and Treatment of Kidney Disease, West Haven, Connecticut 06516 Yale University School of Medicine, New Haven, Connecticut 06520 and West Haven VA Medical Center, West Haven, Connecticut 06516 An edematous patient may be deemed resistant to diuretic drugs when moderate doses of a loop diuretic do not achieve the desired extracellular fluid ECF volume reduction. As shown in Fig. 1, the natriuretic dose-response curve for loop diuretics is sigmoidal the...

Diuretic Use In The Treatment Of Metabolic Alkalosis

It is important to be able to distinguish between the various clinical syndromes associated with metabolic alkalosis before considering the use of diuretics as treatment. In some conditions use of certain diuretics may actually worsen the alkalotic state while in other circumstances certain diuretics may be the preferred mode of therapy Table 4 . In general, the mercurial, thiazide, and loop diuretics have no place in the treatment of metabolic alkalosis. In fact, one of the most common causes...

Ventilatory Acclimatization And Acidbase Homeostasis At Altitude [11

Upon exposure to high altitude, a drop in arterial P02 or 02 saturation stimulates peripheral chemoreceptors and produces an immediate increase in ventilation which raises alveolar P0z PAo2 back toward normal. The beneficial effect of hyperventilation on oxygenation is offset by the rapid development of hy-pocapnia and respiratory alkalosis which in turn blunts further ventilatory response. A biologic compromise is quickly reached where PAo2 is only partially restored and the changes in...

Mechanism Of Action Of Loop Diuretics Effect on Renal Calcium Transport

It has been shown that furosemide inhibits renal calcium reabsorption in the thick ascending limb of Henle. It has been suggested that this inhibitory effect may be due to the abolition by furosemide of normal lumen positive voltage 16 , thereby retarding renal tubular calcium reabsorption. The inhibitory action of furosemide on renal tubular calcium reabsorption in the loop may also be offset by enhanced reabsorption at other sites in proximal tubule in response to volume depletion and in the...

Overhydration

University of Texas, Southwestern Medical Center, Dallas, Texas 75235-8856 Diuretics, especially thiazide diuretics, are a frequent cause of hyponatremia. Paradoxically, loop diuretics can be important adjuncts in the treatment of acute symptomatic hyponatremia, the syndrome of inappropriate secretion of antidiuretic hormone SIADH , and diabetes insipidus. Hyponatremia is caused by water retention due to a continued water intake more than the ability of the kidneys to excrete electrolyte-free...

Diuretics Acting in Late Distal Tubule and Collecting Duct

These diuretics, usually referred to as potassium-sparing diuretics, are divided into two main classes agents whose action does not depend on the inhibition of aldosterone and agents which are classical pharmacological competitive antagonists of aldosterone. Amiloride and triamterene are the main diuretics with action independent of the antagonism of aldosterone. Potassium sparing diuretics are usually administered concomitantly with more potent diuretics to counteract diuretic-induced...

Use Of Albumin And Diuretics For Edema Treatment

Although the combination of albumin and diuretics has been used in the treatment of nephrotic edema for over 25 years, few studies have critically examined the response to this therapy. Most studies report using 0.5-1.0 g kg body weight of 20-25 albumin administered over 30-60 min followed by a 30-min infusion of 1-2 mg kg furosemide. This therapy is then repeated daily or every other day as needed to achieve the desired degree of weight loss. Average weight losses of 1.2 to 2.5 of the initial...

Renal Artery Stenosis

Renal ischemia as a consequence of main or branch artery narrowing causes increased renin production by the affected kidney. This in turn leads to high levels of angiotensin ii which is a potent arterial vasoconstrictor and also stimulates increased aldosterone production see Table 3 . The degree of associated ECV expansion depends on the function of the contralateral kidney. This is an important and increasingly recognized cause of secondary hypertension in older patients because of widespread...

Toxic Agents Drug Overdose Poisons Contrast Media

Nephrology Metabolism Division, Baylor University Medical Center, Dallas, Texas 75246 This chapter focuses on the use of diuretics in the management of life threatening poisonings, drug overdoses, and radiocontrast agent-induced disease. These problems occur relatively frequently and continue to be major challenges for clinicians. Radiocontrast-induced acute renal failure may occur in a hospital setting, especially in an age of more aggressive interventional radiological techniques. This...

Continuous Diuretic Infusion

For hospitalized patients who are resistant to diuretic therapy, another approach is to infuse diuretics continuously. Continuous diuretic infusions have several potential advantages over bolus diuretic administration. First, because they avoid troughs of diuretic concentration, they prevent intermittent periods of positive NaCl balance postdiuretic NaCl retention . When short acting diuretics, such as the loop diuretics, are administered by bolus infusion or by mouth once or twice a day, a...

Mediators Which Stimulate Renal Salt and Water Retention and Constrict Blood Vessels

The major neurohormonal responses which increase renal salt and water retention and cause vasoconstriction are portrayed in Fig. 1. The low EABV associated with heart failure activates sympathetic adrenergic nerves and elevates systemic catecholamine levels which produce both systemic and cardiac effects. Systemic arteriolar constriction mitigates the fall in FIGURE 1. The pathophysiology of salt and water retention and edema formation in patients with heart failure. Only the vasoconstricting...

Renal Insufficiency Table

Renal insufficiency affects the pharmacokinetics of loop diuretics in several ways. All of these drugs but muzolimine, ozolinone, and xipamide are highly bound gt 95 to albumin, thereby preventing filtration at the glomerulus. In azotemic patients, accumulated endogenous organic acids displace these drugs from albumin, increasing the fraction unbound. This effect results in increased amounts of drug reaching the urine by filtration, but the amount is quantitatively negligible compared to that...

Carbonic Anhydrase Inhibitors

A second group of drugs that reduce proximal salt and water absorption are inhibitors of carbonic anhydrase. This enzyme is present on plasma membranes apical and basolateral of proximal convoluted tubule cells and within the cytoplasm. Carbonic anhydrases are produces of a gene family that encodes seven isozymes CA I VII and several homologous carbonic anhydrase-related proteins. All seven isozymes have been cloned, sequenced, and mapped see Table 1 . Types II and IV have been identified in...

Jv K [Pc Pi a Jtc

A schematic diagram of an idealized systemic subcutaneous capillary. The pressure profile along the length of the capillary and in the subcutaneous interstitial space are shown. Capillary hydrostatic pressures fall progressively from 30 to 10 mm Hg. The oncotic pressure of about 28 mm Hg increases trivially along the length of the capillary because the fraction of fluid which is filtered is very small less than 1 . In the arterial portion of the capillary the pressure gradients favor...

The NaK2Cl Cotransporter Genes and Proteins

Major advances have been made over the past few years in our understanding of the actions of loop diuretics. This is due in large part to the molecular identification of a family of cationchloride cotransporters to which the Na K 2C1 transporters belong see Table 2 . This information has revolutionized our thinking about these transporter proteins. It is now clear that Na K 2C1 co-transport activity is the function of a single membrane protein, dispelling the earlier speculations that a complex...

Renal Transport Of Anionic Diuretics

Three steps are necessary to effect tubular secretion of organic anions. First, the anionic compound must be delivered to the basolateral surface of the proximal tubule cell second, the anionic compound must be transported into the cell across the basolateral membrane and third, the anionic compound must be transported across the brush border membrane into the tubule lumen. Most investigations of these processes relating to anionic diuretic secretion have used furosemide and chlorothiazide as...

Diuretic Pharmacokinetic And Pharmacodynamics In Renal Insufficiency

Diuretic Dose Response Curve

Both pharmacokinetic and pharmacodynamic mechanisms contribute to the reduced efficacy of loop diuretics in chronic renal disease. Several pharmacokinetic mechanisms limit delivery of diuretic to its active site. First, as renal blood flow is reduced in parallel to glomerular filtration rate GFR , delivery of diuretic to the organic acid transport system in the proximal tubule is delayed. Additionally some uremic toxins are organic anions and can competitively inhibit tubular diuretic...

Diet and Bed Rest

The safest and most conservative treatment of cirrhotic ascites and edema is the institution of bed rest and a low salt diet. This regimen will produce significant clinical improvement in 20-30 of cirrhotic patients 7 . Bed rest reduces lower extremity venous pooling, shifts some blood from splanchnic to central vessels, and expands the EABV. Although bed rest clearly promotes diuresis and natriuresis, it is only a temporizing maneuver. Restricting salt intake below the rate of renal excretion...

Arterial Pressure

Both thiazide and loop diuretics reduce arterial pressure in hypertension. Although neither group of agents is noted for its ability to reduce arterial blood pressure in heart failure they almost certainly contribute to the low arterial pressure commonly seen in this condition. Diuretics reduce arterial pressure Diuretic Agents Clinical Physiology and Pharmacology Copyright 1997 by Academic Press. All rights of reproduction in any form reserved. despite activation of neuroendocrine...

Endogenous Ouabain

In the 1960s and 1970s, de Wardener and colleagues developed evidence for the existence of various natriuretic factors, which could stimulate salt excretion in the setting of volume expansion by inhibition of tubule Na K ATPase 16 . While numerous extracts of plasma and urine from volume expanded animals inhibited Na K ATPase activity and reduced transepithelial Na transport in a number of renal model epithelia, the identity of these factors remained unclear 16 , Recent studies have provided...

Mechanism Of Action Of Amiloride Effect on Renal Calcium Transport

Amiloride inhibits sodium transport in the late distal tubules, likely connecting tubules, and other epithelial cells by blocking sodium channels 4 . Recently, it has been shown that amiloride inhibits sodium entry into the cells and hyper-polarizes the luminal and basolateral membranes. The latter effect, in turn, stimulates calcium influx into the cells and produces a sustained rise of intracellular calcium concentration. Calcium influx and rise of intracellular calcium concentration is...

Broader Definition Of Hypertension

'A low, or declining, diastolic blood pressure has been linked to vessel wall thickening associated with progression of atherosclerosis and therefore may be an indication of widespread arterial disease and increased risk of cardiovascular mortality. 65 70 75 80 85 90 95 100 105 110 115 FIGURE 3. The J-curve for cardiovascular mortality and diastolic blood pressure DBP . Low DBP may be a consequence rather than a cause of increased mortality. 65 70 75 80 85 90 95 100 105 110 115 FIGURE 3. The...

Dopamine And Dobutamine For Congestive Heart Failure

Acute dopamine infusion increases renal plasma flow, urinary sodium excretion rate, glomerular filtration rate, and the functional status of patients with moderate to severe congestive heart failure. These effects result from stimulation of dopamine receptors DA and DA2 as well as f3 adrenergic receptors. Beregovich and co-workers 2 studied the dose-related hemodynamic and renal effects of dopamine in patients with classes III and IV congestive heart failure see Fig. 5 . Cardiac output and...