Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

About 40% of the intoxications after drug administration occur in the elderly. A significant proportion of the disease states in elderly patients is related to adverse reactions to prescribed drugs. Declining renal function, a reduction in both renal blood flow and glomerular filtration rate, is a major contributor to drug toxicity in the elderly. Therefore, a review (based on newer papers from Medline) of age-dependent changes of the kidneys and their consequences for drug therapy in geriatric patients is presented. Renal changes that occur with aging are: a decrease of renal weight, a thickening of the intrarenal vascular intima, sclerogenous changes of the glomeruli, and infiltration of chronic inflammatory cells and fibrosis in the stroma. Altered renal tubular function, including impaired handling of water, sodium, acid, and glucose, is also frequently present in old age. Impaired 'endocrinologic' functioning manifested by changes of the renin-angiotensin system, vitamin D metabolism, and antidiuretic hormone responsiveness has been reported. The aging kidney is constantly exposed to the effects of a variety of potential toxic processes, i.e., drugs and chronic illnesses including hypertension, diabetes, and atherosclerotic disease. Renal changes that occur with aging also consist of impairment in the ability to concentrate urine and to conserve sodium and water. These physiological changes increase the risks of volume depletion and prerenal type of acute renal failure. A frequent cause of acute renal failure in the elderly is drug-induced nephropathy. Nonsteroidal anti-inflammatory drugs, antibiotics, and diuretics are most often involved. Due to the age-dependent decline of renal function, the pharmacokinetics of many drugs are altered in elderly patients. Therefore, the most important renal function to monitor with aging is the creatinine clearance. Changes in pharmacokinetics of many drugs and most decisions on drug dosage can be based on this information alone, as tubular functions of the kidney decrease at rates paralleling the age-dependent decrease in glomerular filtration rate (which is approximately measured by the creatinine clearance). As a conclusion, age-dependent changes of renal function are not only responsible for changes in pharmacokinetics and pharmacodynamics. In many cases, the kidneys are the target organ of adverse drug reactions too.
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PMID:Age-dependent changes of the kidneys: pharmacological implications. 1046 Sep 85

In puromycin aminonucleoside (PAN)-treated nephrotic rats, sodium retention is associated with increased (Na+/K+)-ATPase activity in the cortical collecting ducts (CCD). This study was undertaken to determine whether stimulation of (Na+/K+)-ATPase in the CCD is a feature of other experimental nephrotic syndromes, whether it might be responsible for renal sodium retention, and whether it is mediated by increased plasma vasopressin levels or activation of calcineurin. For this purpose, the time courses of urinary excretion of sodium and protein, sodium balance, ascites, and (Na+/K+)-ATPase activities in microdissected CCD were studied in rats with PAN or adriamycin nephrosis or HgCl2 nephropathy. The roles of vasopressin and calcineurin in PAN nephrosis were evaluated by measuring these parameters in Brattleboro rats and in rats treated with cyclosporin or tacrolimus. Despite different patterns of changes in urinary sodium and protein excretion in the three nephrotic syndrome models, there was a linear relationship between CCD (Na+/K+)-ATPase activities and sodium excretion in all three cases. The results also indicated that there was no correlation between proteinuria and sodium retention, but ascites was present only when proteinuria was associated with marked reduction of sodium excretion. Finally, the lack of vasopressin in Brattleboro rats or the inhibition of calcineurin by administration of either cyclosporin or tacrolimus did not prevent development of the nephrotic syndrome in PAN-treated rats or stimulation of CCD (Na+/K+)-ATPase. It is concluded that stimulation of Na(+/K+)-ATPase in the CCD of nephrotic rats might be responsible for sodium retention and that this phenomenon is independent of proteinuria and vasopressin and calcineurin activities.
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PMID:Collecting duct (Na+/K+)-ATPase activity is correlated with urinary sodium excretion in rat nephrotic syndromes. 1075 19

Angiotensin II receptor antagonists (AT-1) represent a new group of orally active antihypertensive agents. Activation on AT-1 receptor leads to vasoconstriction, stimulation of the release of catecholamines and antidiuretic hormone with production of thirst, and promote growth of vascular and cardiac muscle; these effects are blocked by AT-1 antagonist agents. The first chemically useful, orally active AT-1 receptor antagonist was losartan, followed by other agents currently in clinical use, such as: valsartan, eprosartan, irbesartan, telmisartan, candesartan, and many others under investigation. AT-1 receptor antagonists are effective in reducing high blood pressure in hypertensive patients. Monotherapy in mild to moderate hypertension controls blood pressure in 40 to 50% of these patients; when a low dose of a thiazide diuretic is added, 60 to 70% of patients are controlled. The efficacy is similar to angiotensin-converting enzyme inhibitors, diuretics, calcium antagonists and beta-blocking agents. Tolerability has been reported to be very good. AT-1 receptor antagonists would be a drug of choice in otherwise well-controlled hypertensive patients treated with angiotensin-converting enzyme inhibitors who developed cough or angioedema. The final position in the antihypertensive therapy in this special population and other clinical situations, such as left ventricular hypertrophy, heart failure, diabetes mellitus and renal disease, has to be determined in large prospective clinical trials, some of which are now being conducted.
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PMID:Angiotensin II receptor antagonists in arterial hypertension. 1085 84

Endothelins are a family of peptides, which comprises endothelin-1 (ET-1), endothelin-2 (ET-2) and endothelin-3 (ET-3), each containing 21 amino-acids. ET-1 is a peptide secreted mostly by vascular endothelial cells, the predominant isoform expressed in vasculature and the most potent vasoconstrictor currently known. ET-1 also has inotropic, chemotactic and mitogenic properties. In addition, it influences salt and water homeostasis through its effects on the renin-angiotensin-aldosterone system (RAAS), vasopressin and atrial natriuretic peptide and stimulates the sympathetic nervous system. The overall action of endothelin is to increase blood pressure and vascular tone. Therefore, endothelin antagonists may play an important role in the treatment of cardiac, vascular and renal diseases associated with regional or systemic vasoconstriction and cell proliferation, such as essential hypertension, pulmonary hypertension, chronic heart failure and chronic renal failure. Long-term anti-endothelin therapy may improve symptoms and favourably alter the progression of heart failure. Endothelin appears to participate in induction and progression of sclerotic renal changes, leading to progression to end-stage renal disease. Anti-endothelin therapy might offer additional benefits in the prevention of progression of chronic renal failure in addition to the known benefits of RAAS inhibition. Clinical trials have demonstrated potentially important benefits of endothelin antagonists for patients with essential hypertension, pulmonary hypertension and heart failure. Further studies are necessary to determine the role of anti-endothelin therapy in the treatment of cardiovascular diseases and determine the different roles of selective receptor antagonism vs. mixed ET(A/B)-receptor antagonism in human diseases.
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PMID:Role of endothelin in cardiovascular disease. 1198 41

Angiotensin II receptor blockers represent a class of effective and well tolerated orally active antihypertensive drugs. Activation of AT(1) receptors leads to vasoconstriction, stimulation of the release of catecholamines and antidiuretic hormone and promote growth of vascular and cardiac muscle. AT(1) receptor blockers antagonise all those effects. Losartan was the first drug of this class marketed, shortly followed by valsartan, irbesartan, telmisartan, candesartan, eprosartan and others on current investigation. All these drugs have the common properties of blockading the AT(1) receptor thereby relaxing vascular smooth muscle, increase salt excretion, decrease cellular hypertrophy and induce antihypertensive effect without modifying heart rate or cardiac output. Most of the AT(1) receptor blockers in use controlled blood pressure during the 24 h with a once-daily dose, without evidence of producing tolerance to the antihypertensive effect and being with low incidence of side effects even at long term use. Monotherapy in mild-to-moderate hypertension controls blood pressure in 40 to 50% of these patients; when a low dose of thiazide diuretic is added, 60-70% of patients are controlled. The efficacy is similar to angiotensin-converting enzyme (ACE) inhibitors, diuretics, calcium antagonists and beta-blocking agents. AT(1) receptor blockers are specially indicated in patients with hypertension who are being treated with ACE inhibitors and developed side effects such as, cough or angioedema. The final position in the antihypertensive therapy in this special population and other clinical situations, such as left ventricular hypertrophy, heart failure, diabetes mellitus and renal disease, has to be determined in large prospective clinical trials, some of which are now being conducted and seem promising.
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PMID:Angiotensin II receptor antagonists role in arterial hypertension. 1198 4

The Authors report 3 cases with clinical renal manifestations where the indication to perform a renal biopsy was defined as borderline. The uncertain indication was related to the clinical presentation, with a pattern of urinary abnormalities, such as isolated microscopic hematuria, microscopic hematuria associated with mild proteinuria, and isolated proteinuria. In addition, similar questions on biopsy are raised for chronic renal failure and elderly patients. In the literature, microscopic hematuria without significant proteinuria shows that 25% of adult patients have no histological abnormalities. A higher percentage is found among children. The other cases exhibit a pattern of IgA nephropathy, Alport's syndrome, thin BM nephropathy and arteriolar C3 deposition. The percentage of an abnormal histological picture increases if the patients have a family history of hematuria, and if there are concomitant episodes of macroscopic hematuria, because of an increase in IgA nephropathy and Alport's syndrome, respectively. In the last cases, therefore the indication to perform a renal biopsy increases. For those patients without these characteristics, a renal biopsy can be delayed whereas in cases of microscopic hematuria with proteinuria or isolated proteinuria the indication for a renal biopsy is stronger, because the spectrum of glomerulopathies is wider, and the possible evolution to renal failure after 10 years is higher (10-14% of cases). In patients with chronic renal failure the biopsy is contraindicated for cases where the thickness of the cortical section of the kidney is lower than 8-10 mm, because of possible technical difficulties, lower diagnostic information due to sclerosis and higher risk of complications. The prolonged bleeding time and the consequent risk of bleeding can be avoided by i.v. infusion of vasopressin 2 hours prior to biopsy. The higher indications are for those patients who may be susceptible to a medical treatment, capable to slowing down the progression of nephropathy. Finally, in elderly patients the biopsy is indicated in almost all cases because of the recently confirmed high incidence of glomerulopathies. In the aged there is a higher frequency of membranous GN, crescentic-ANCA associated GN, amyloidosis and, according to some Authors, post-infectious GN. In all cases a precise histological diagnosis can correct an erroneous diagnosis made according to clinical data alone. In the elderly the indication for biopsy aims at making an exact diagnosis of nephropathy, especially for acute renal failure: for this purpose age itself should not become an obstacle.
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PMID:[Borderline indications for renal biopsy]. 1219 3

Senescent female WAG/Rij rats exhibit polyuria without obvious renal disease or defects in vasopressin plasma level or V(2) receptor mRNA expression. Normalization of urine flow rate by 1-desamino-8-d-arginine vasopressin (dDAVP) was investigated in these animals. Long-term dDAVP infusion into 30-mo-old rats reduced urine flow rate and increased urine osmolality to levels comparable to those in control 10-mo-old rats. The maximal urine osmolality in aging rat kidney was, however, lower than that in adult kidney, despite supramaximal administration of dDAVP. This improvement involved increased inner medullary osmolality and urea sequestration. This may result from upregulation of UT-A1, the vasopressin-regulated urea transporter, in initial inner medullary collecting duct (IMCD), but not in terminal IMCD, where UT-A1 remained low. Expression of UT-A2, which contributes to medullary urea recycling, was greatly increased. Regulation of IMCD aquaporin (AQP)-2 (AQP2) expression by dDAVP differed between adult and senescent rats: the low AQP2 abundance in senescent rats was normalized by dDAVP infusion, which also improved targeting of the channel; in adult rats, AQP2 expression was unaltered, suggesting that IMCD AQP2 expression is not regulated by dDAVP directly. Increased AQP3 expression in senescent rats may also be involved in improved urine-concentrating capacity owing to higher basolateral water and urea reabsorption capacity.
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PMID:Correction of age-related polyuria by dDAVP: molecular analysis of aquaporins and urea transporters. 1238 83

The antimalaria drug chloroquine is often taken against a background of analgesic nephropathy caused by nonsteroidal anti-inflammatory drugs such as paracetamol (acetaminophen). Chloroquine has marked effects on the normal kidney and stimulates an increase in plasma vasopressin via nitric oxide. The aim of this study was to determine the renal action of chloroquine in a model of analgesic nephropathy. Sprague-Dawley rats (n = 6-8/group) were treated with paracetamol (500 mg kg(-1) day(-1)) for 30 days in drinking water to induce analgesic nephropathy; control rats received normal tap water. Under intraval anesthesia (100 mg kg(-1)) rats were infused with 2.5% dextrose for 3 h to equilibrate and after a control hour they received either vehicle, chloroquine (0.04 mg h(-1)), N(omega)-nitro-L-arginine methyl ester (L-NAME, nitric-oxide synthase inhibitor, 60 micro g kg(-1) h(-1)) or combined chloroquine and L-NAME over the next hour. Plasma was collected from a parallel group of animals for vasopressin radioimmunoassay. Long-term paracetamol treatment resulted in a decrease in glomerular filtration rate (p < 0.05), sodium excretion (p < 0.001), and urine osmolality (p < 0.001), but no change in urine flow rate compared with untreated animals. Chloroquine administration in paracetamol treated rats induced a significant reduction (p < 0.05) in urine flow rate and a significant increase in plasma vasopressin (p < 0.001). These effects were blocked by coadministration of L-NAME and thus seem to be mediated by a pathway involving nitric oxide. However, these responses contrast with the chloroquine-induced diuresis previously observed in untreated rats, possibly reflecting paracetamol inhibition of renal prostaglandin synthesis and consequent moderation of vasopressin's action.
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PMID:Renal function in a rat model of analgesic nephropathy: effect of chloroquine. 1264 60

Based on the progress made during the last few years in understanding the pathophysiology of acute renal failure, a plethora of therapeutic drug and nondrug interventions have been developed and tested in animal and human forms of this disease. The first part of this article focuses on the role of volume expansion and vasopressors in the prevention and treatment of acute renal failure in the critically ill. From all prophylactic measures that have been proposed, volume expansion, or at least correction of volume depletion, remains the most efficient and most evidence-based intervention in these patients. Norepinephrine is, out of all the vasopressors, probably the most appropriate to use in cases of hypotension, provided circulating volume is adequate. In hypotensive septic patients, vasopressin has been shown to be useful. Direct renal vasodilating substances, the most popular still being low-dose dopamine, have never been proved to be useful in carefully performed prospective trials. Moreover dopamine especially is associated with a number of side effects and complications. From the agents acting on tubular factors, the diuretic mannitol and loop diuretics are the most prescribed. Only in specific situations such as rhabdomyolysis and kidney transplant surgery has it been shown that mannitol was able to prevent acute renal failure. The loop diuretics are able, after establishing adequate circulating volume, to promote diuresis in some forms of oliguric acute renal failure; however, some recent papers have shown that the administration of loop diuretics may actually be associated with increased mortality and delayed recovery of renal function. The last few years have seen a number of trials with acetylcysteine in the prevention of mainly radiocontrast nephropathy. Although the results are still conflicting, the majority indicates that acetylcysteine, when applied together with adequate volume expansion, may be a useful drug to incorporate in the standard treatment procedures in patients at risk for acute renal failure. Interventions to stimulate the recovery process of the damaged kidney with growth factors, although theoretically sound, have thus far not led to successful results.
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PMID:Prevention and nondialytic treatment of acute renal failure. 1463 67

We describe a case of severe hyponatremia following chemotherapy administration in a patient with small-cell lung cancer. There was no evidence of the syndrome of inappropriate antidiuretic hormone (SIADH) secretion. The clinical and laboratory findings were consistent with a sodium-wasting nephropathy complicating cisplatin administration. There are few well-documented reports of cisplatin-associated hyponatremia in the medical literature. We have summarized the relevant literature and attempted to define the differential diagnosis of hyponatremia in this setting. Most cases are accounted for by sodium-losing nephropathy of SIADH, but many reported cases contain insufficient data for classification. Appropriate attention to the evaluation of hyponatremia following platinum-based chemotherapy is needed to properly treat these conditions.
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PMID:Sodium-wasting nephropathy caused by cisplatin in a patient with small-cell lung cancer. 1466 76


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