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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Isolated kidneys taken from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) were perfused over a range of perfusion pressures. 2. Lithium clearance was used as an index of proximal tubule sodium handling. 3. When the perfusate contained an oncotic agent (albumin, 6.7 g/dl) the SHR kidneys performed differently from the WKY kidneys with a reduction in inulin clearance, sodium excretion, fractional sodium excretion and fractional lithium excretion [at 105 mmHg (14 kPa) perfusion pressure, SHR 6.0 +/- 1.1% vs WKY 12.6 +/- 2.4% (mean +/- SEM); at 150 mmHg (20 kPa), SHR 17.1 +/- 1.6% vs WKY 27.0 +/- 2.3%]. Calculated indices of distal tubular function showed no major differences between SHR and WKY. 4. When kidneys were perfused without oncotic agent in the perfusate the differences between SHR and WKY in tubular handling of sodium and lithium were largely abolished. 5. These findings are consistent with the hypothesis that increased sodium reabsorption occurs in the proximal tubules of the kidneys of SHR and suggest that this is an intrinsic property of the kidney, not immediately dependent on neural or humoral factors. Increased sodium reabsorption in the proximal tubule may contribute significantly to the existence of hypertension in the SHR.
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PMID:Sodium and lithium handling in the isolated hypertensive rat kidney. 292 26

Twenty-five years after the discoveries of the existence of atrial granules and of volume receptors in the heart atria the search for natriuretic hormones has led to the isolation and identification of the atrial natriuretic factors (ANF) now considered as a hormonal system. These peptides are probably synthesized and stored in the Golgi apparatus of cardiac myocytes and are released in response to atrial wall stretch following acute plasma volume expansion and increased central blood volume, e.g., during head-out water immersion, in arterial hypertension, or increased left and/or right atrial pressure in cardiac failure, but also possibly in response to increased frequency of myocardial contractions, e.g. in paroxysmal tachycardia. The mechanisms of the renal action of these potent natriuretic hormones are not yet precisely known. Increased GFR may contribute to the initial rise in urinary sodium excretion and increased renal medullary blood flow to the later phase of natriuresis. The proximal tubule, the thin descending and the ascending limb of Henle's loop and especially the medullary collecting tubule were so far incriminated as tubular sites of action of ANF. Finally, recycling of sodium in medullary tissue and secretion of sodium via back-flux from the interstitium into the medullary collecting tubule are postulated to result in the hypernatric urine observed after ANF administration. Direct suppression of the secretion of renin, aldosterone, vasopressin, and vasopressin-stimulated cAMP synthesis may also contribute to its diuretic, natriuretic, and antihypertensive effects. The renal hemodynamic and tubular as well as the adrenal and systemic vascular effects are related to enhanced cGMP synthesis in medium-sized arterial vessels, in glomeruli and specific tubular segments, and in adrenal tissue, and may be calcium dependent. Specific ANF-binding sites were detected in these target organs. Although increased ANF release was observed in response to atrial distension in various disease states, which may contribute to renal sodium elimination in human hypertension and congestive heart failure, further studies are needed to identify its precise physiological and pathophysiological significance.
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PMID:Atrial natriuretic hormones--thirty years after the discovery of atrial volume receptors. 294 41

Several steroid hormones act in the kidney. We have examined, by autoradiography, the precise distribution of receptors for aldosterone, glucocorticoids, vitamin D (1-25(OH)2D3) and estrogens, in the different epithelia of the nephron isolated by microdissection. Specific nuclear binding sites are localized in the distal parts of the nephron, with some variations according to the steroid hormone considered: target cells for aldosterone are located in the distal tubule and cortical collecting duct, glucocorticoid receptors are present in all distal segments, whereas those of 1-25(OH)2D3 are restricted to the thick ascending limb of Henle's loop and to the medullary collecting tubule. Thus, it appears that several receptors coexist in some cell types. No specific nuclear binding sites for estrogens could be detected along the nephron. On the other hand, a non nuclear specific binding for glucocorticoids was observed in the proximal tubule, where specific glucocorticoid effects have been described. By autoradiography on intact target cells, it appeared that aldosterone receptors are essentially (or exclusively) located in nuclei, as was recently described for other steroid hormones. Binding sites for aldosterone are already present in its target cells in the fetal kidney before their functional differentiation. Aldosterone is weakly metabolized in the kidney, without specific tubular localization. It is possible to show some modifications of aldosterone binding sites, at the level of its target cells, in some pathological states, such as hypertension.
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PMID:[Receptors of steroid hormones in the kidney]. 304 46

Indomethacin and some other nonsteroidal anti-inflammatory drugs partially antagonize the blood pressure lowering effect of drugs used to treat hypertension. They can also produce a mild elevation of blood pressure in normotensive individuals. The elevated arterial pressure caused by these agents is associated with increases in the vascular resistance of mainly the renal and splanchnic beds. This may be due to direct inhibition of the synthesis of vasodilator prostanoids, or it may be due to indirect potentiation of the action of the sympathetic nervous system or of angiotensin II. Nonsteroidal anti-inflammatory drugs also cause renal retention of sodium and this probably contributes to their hypertensive effects. In humans, the sodium retention may involve increased reabsorption in the proximal tubule. Although a direct tubular action is possible, these drugs may change proximal sodium reabsorption by their vascular effects. However, the exact mechanism is not understood. These interactions are clinically significant and may complicate the treatment of common diseases.
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PMID:Interaction of nonsteroidal anti-inflammatory drugs with antihypertensive and diuretic agents. Control of vascular reactivity by endogenous prostanoids. 309 65

Since hypertension is associated with changes in the handling of various cations (including sodium and lithium) across the cell membrane, the present study investigated the validity of the lithium clearance method in hypertension by comparing two measures of proximal reabsorption. Thus, fractional lithium excretion and transit time (TT)-occlusion time (OT; e-TT/T) were determined successively in the same spontaneously hypertensive rat (SHR, Okamoto strain). The rats were examined both before and after an acute saline load. The results show that the lithium clearance method can be used for the determination of proximal reabsorption in SHR. Utilizing the lithium clearance method, the changes in renal sodium handling underlying the exaggerated natriuresis were investigated in unanaesthetized catheterized rats. It was found that the exaggerated natriuresis was associated with an increased output from the proximal tubule, whereas no difference in distal sodium handling could be detected between SHR and normotensive Wistar-Kyoto rats (WKY).
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PMID:Exaggerated natriuresis and lithium clearance in spontaneously hypertensive rats. 323 36

Acute hypertension was previously shown to cause partial inhibition of proximal tubule fluid reabsorption in perfused tubules in the rat. If the inhibition also occurs in unobstructed tubules receiving native glomerular filtrate, hypertension should increase end proximal flow rate despite autoregulation of glomerular filtration rate (GFR). We tested this prediction with a videodensitometric method recently developed for measurement of tubular flow rate that does not interrupt flow to the macula densa. Hypertension was induced by increasing total peripheral resistance in rats receiving several hormones at rates designed to maintain high levels of these agents. End proximal flow rate was increased 18% as early as 1.5-2 min following the induction of hypertension and increased over the course of the next 25-30 min to reach values 50% greater than controls as the hypertension was sustained. Whole-kidney GFR and renal blood flow were fully autoregulated. The results confirm that hypertension increases the fluid load to the loop of Henle, and are consistent with an effect on proximal tubule fluid reabsorption. This increase in fluid load could signal the macula densa and contribute to the efficacy of autoregulation; it could also provide a significant fraction of the increased fluid and salt excretion of pressure natriuresis.
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PMID:Time course of proximal tubule response to acute arterial hypertension in the rat. 335 89

Micropuncture experiments were performed in volume-expanded rats to better define the nephron segments in which changes in renal perfusion pressure inhibit tubular reabsorption. Neural influences on the kidney were eliminated by renal denervation, and plasma levels of vasopressin, aldosterone, corticosterone, and norepinephrine were maintained at fixed levels by i.v. infusion. Fractional excretion of sodium, chloride, and water increased markedly after renal perfusion pressure was elevated from 110 to 150 mm Hg. Renal blood flow, glomerular filtration rate, and single nephron glomerular filtration rate measured from deep and superficial nephrons were unsaltered. Reabsorption of chloride and water in the proximal tubule of superficial nephrons decreased by 10% after renal perfusion pressure was elevated and contributed to the pressure-diuretic response. Changes in renal perfusion pressure also altered the reabsorption of water and chloride in juxtamedullary nephrons. The percentage of the filtered water load reaching the tip of the loop of Henle increased from 19.8 +/- 2.9 to 38.1 +/- 3.0% after renal perfusion pressure was elevated. Chloride delivery rose from 34.2 +/- 4.3 to 65.2 +/- 4.8% of the filtered load. These results support the view that alterations in medullary hemodynamics participate in the pressure-natriuretic response by inhibiting tubular reabsorption in the proximal tubule or the thin descending limb of the loop of Henle (or both) of juxtamedullary nephrons.
Hypertension 1988 Aug
PMID:Pressure-diuresis in volume-expanded rats. Tubular reabsorption in superficial and deep nephrons. 341 May 26

To investigate renal tubular handling of sodium in various types of experimental hypertension, sodium, lithium, and inulin clearances were measured simultaneously in unanesthetized rats. Fractional excretion of lithium was used as an index of proximal sodium reabsorption. Eight groups of animals, all of the Wistar-Kyoto strain, were studied. Three were hypertensive: spontaneously hypertensive rats (SHR), rats with two-kidney, one clip renal hypertension, and uninephrectomized rats with deoxycorticosterone-salt hypertension. The five normotensive control groups included animals given normal, low, or high dietary sodium loads and rats with reduced renal mass. Fractional excretion of lithium was not influenced by moderate changes of glomerular filtration rate, but was sharply enhanced by sodium loading. Increased blood pressure was associated with enhanced urinary sodium excretion in uninephrectomized deoxycorticosterone-salt hypertensive and two-kidney, one clip hypertensive rats, as a result of decreased distal tubular reabsorption ("pressure natriuresis"). In contrast, SHR showed reduced sodium excretion and decreased fractional excretion of lithium, which suggests that increased sodium reabsorption in the proximal tubule may contribute significantly to the maintenance of hypertension.
Hypertension 1986 Feb
PMID:Lithium infusion to study sodium handling in unanesthetized hypertensive rats. 351 Sep 75

Microaspiration techniques and clearance studies have shown that reabsorption of filtered sodium approximates 65% in the proximal tubule, 25 to 30% in the ascending limb of the loop of Henle and 5 to 10% in the dilution segment. Reabsorption in the Henle loop is of special significance as it governs the process of dilution-concentration of urine. Moreover, inhibition of sodium reabsorption in the loop of Henle necessarily produces a substantial loss of sodium since only a fairly small fraction of urinary sodium is reabsorbed beyond the Henle loop (dilution segment, distal tubule). Excretion of water and electrolytes is regulated by humoral factors, such as the renin-angiotensin-aldosterone system, some prostaglandins and certain kinins. Factors that promote excretion of sodium, produced in particular by the myocardium, have recently been demonstrated. The correlation between blood pressure and salt has been substantiated by many findings. Diuretics are commonly used to treat high blood pressure as well as edema. Recent evidence indicates that sodium transport is altered in idiopathic hypertension, at least in red blood cells. Clinical trials of diuretics are designed to localize the drug's action and quantify its saluretic activity (evaluation of potency and effectiveness--single doses, sustained treatment). Furthermore, the minimal efficient antihypertensive dosage should be determined. Diuretics can be divided into two groups according to whether they produce an increase or decrease in serum potassium. Diuretics that are capable of producing hypokalemia belong to two main families. One consists of the Henle loop diuretics that interfere with the mechanisms of dilution-concentration of urine. Action of these drugs is potent and short-lived. For instance, following a single dose of furosemide, excretion of sodium can reach 25-30% of filtered sodium; renal blood flow increases; CH2O and TCH2O decrease. With furosemide, induction of diuresis is rapid (within a few minutes after IV injection and 20 mn after oral ingestion); elimination half-life is 50 mn; absolute bioavailability is 50-70%; 95% of the drug is bound to plasma proteins; elimination is mainly through the kidneys. Other Henle loop diuretics include ethacrynic acid, whose elimination half-life is less than one hour; bumetanide, which is 40 times more potent than furosemide; muzolimine, whose action is more lasting despite the fact that only 65% of the drug is bound to plasma proteins; and ozolinone, which has a saliuretic action comparable to that of furosemide and in addition exerts a direct vasodilating effect.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Diuretics]. 353 32

Although cyclosporine (CsA) therapy has improved the outcome of allotransplantation, drug-induced nephrotoxicity presents a potentially serious complication in a significant proportion of patients. The nephrotoxic injury, which may present acutely in the peritransplant period, subacutely in the first few months, or chronically, may be caused by toxic effects at various levels of the nephron: arteriole, glomerulus, and/or proximal tubule. The nephrotoxic picture of decreased glomerular filtration rate, impaired urea secretion, hyperkalemia, hypertension, and tubular dysfunction with preserved sodium reabsorption occurs not only in the renal allotransplant setting, wherein it obscures the diagnosis of rejection, but also in recipients of other grafts and patients under treatment for autoimmune disease. Because conversion from CsA to other immunosuppressive agents carries a high risk of rejection and allograft loss (or recrudescence of autoimmune disease), the present management strategy uses cautious CsA does reduction with concomitant institution of full-dose azathioprine (Aza) therapy. Definition of pharmacokinetic and pharmacodynamic properties that predict patients at risk for nephrotoxic complications may lead to new CsA dosing regimens yielding an improved therapeutic index.
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PMID:Cyclosporine nephrotoxicity: pathogenesis, prophylaxis, therapy, and prognosis. 353 56


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