Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1 Twelve patients with mild hypertension were treated with bumetanide for a six-month period. No evidence was found of hypokalaemia or decreased total exchangeable potassium in subjects with or without additional potassium supplements. 2 Bumetanide was well tolerated by all patients. It caused hyperuricaemia but no episodes of gout occurred. Minor abnormalities of liver function were noted. 3 Bumetanide did not have a sustained antihypertensive action.
 ...
PMID:Lack of effect of bumetanide on body potassium content in hypertension. 123 92

Sodium and potassium ion transport systems were studied in erythrocytes from spontaneously hypertensive Okamoto rats (SHR), hypertension-prone Sabra rats (SbH), and one-kidney one-clip Goldblatt hypertensive rats, and compared with Wistar-Kyoto normotensive rats (WKY), hypertension-resistant Sabra rats (SbN), and sham-operated Wistar rats. We observed the following: (1) An increased net potassium influx and a reduced net sodium extrusion occurred in SHR. The increased potassium influx was inhibited by ouabain, indicating an increased sodium ion pump activity. Bumetanide-sensitive sodium extrusion was lower in SHR than it was in WKY, indicating abnormally low outward sodium-potassium cotransport fluxes. (2) Passive sodium ion permeability was increased in SbH compared with SbN. Cotransport was normal in SbH rats. (3) Sodium-potassium cotransport and passive permeability were normal in renovascular hypertension. (4) After a chronic or acute sodium load, the sodium content increased in erythrocytes from SHR and SbH but not in those of normotensive or renal hypertensive rats. It appears therefore that erythrocyte membrane abnormalities leading to an increased intracellular sodium concentration are only present in genetic hypertension. The reduction of outward sodium-potassium cotransport observed in SHR is identical to that previously reported in human essential hypertension, suggesting that it may be considered as a genetic marker.
 ...
PMID:Erythrocytic sodium ion transport systems in primary and secondary hypertension of the rat. 695 75

Bumetanide was compared with furosemide in a total of 43 outpatients with edema due to renal disease, selected from three clinics following a uniform protocol. By random selection, 31 patients received 1 to 10 mg/day bumetanide, and 12 received 40 to 400 mg/day furosemide for at least six months. The patients were evaluated clinically, by standard laboratory tests, as well as by ECG, audiometry, eye examination, and mammary examination. Pooled statistical analysis of the results was done. Edema, body weight, and abdominal girth were reduced during both treatments. There was no significant difference in the mean response to the two diuretic agents by the two sided probability test in the other parameters studied, e.g., supine and standing blood pressure and pulse, serum electrolytes (sodium, potassium, chloride), and uric acid. There were no differences in liver function tests, hematology, or chest x-ray, and no remarkable effects on hearing. Gynecomastia improved in some patients while being treated with bumetanide after spironolactone was discontinued. Adverse reactions in patients on bumetanide which were considered possibly or probably related to the drug were muscle cramps (two patients); and vertigo, headache, muscle pain, urticaria, chest pain, arthritis, dehydration, postural hypotension, and leg cramps (one each). Laboratory abnormalities in both groups were generally those that could be attributed to the pharmacologic action of the diuretics or due to the patients' underlying disease states. No drug-related adverse effects were noted in ECG, ophthalmologic examinations, or chest x-rays. Two patients in the furosemide group had a probably or possibly drug-related loss of hearing sensitivity. In summary, bumetanide appeared to be as safe and as efficacious as furosemide in controlling edema and hypertension in patients with renal disease.
 ...
PMID:Long-term bumetanide treatment of patients with edema due to renal disease. Cooperative studies. 704 Apr 92

Bumetanide is a loop diuretic that is used for the treatment of edema and hypertension. The rapidly developing syndrome of extracellular fluid overload in some malnourished children has been successfully treated with furosemide, another loop diuretic, and digoxin; however, similar studies with bumetanide have not been conducted to date. Therefore, in the present study, the influence of dietary protein deficiency on the pharmacokinetics and pharmacodynamics of bumetanide was investigated after intravenous (i.v.) bolus and oral administration of bumetanide to male Sprague-Dawley rats fed on 23% (control rats) or 5% [protein and calorie malnutrition (PCM) rats] protein diet ad libitum for 4 weeks. After an i.v. dose of bumetanide, 1 mg/100 g body weight, the mean values of renal clearance and percentages of dose excreted as unchanged bumetanide in an 8-h urine sample were 166 and 154% higher, respectively, in PCM than control rats; however, nonrenal clearance (CLNR) was 28% lower. The decrease in nonrenal clearance in PCM rats might be because of the decrease in nonrenal metabolism of bumetanide in PCM rats. The urine output per 100 g of body weight was not significantly different between the two groups of rats after i.v. administration, although the amount of bumetanide excreted in the 8-h urine sample per 100 g body weight increased significantly in PCM rats. These results could be explained by the fact that the dose of bumetanide used results in urinary excretion rate of bumetanide at the plateau of the concentration-effect relationship.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Influence of protein and calorie malnutrition on the pharmacokinetics and pharmacodynamics of bumetanide in rats. 837 24

Recently the molecular identification of the major electroneutral sodium-potassium-chloride entry mechanisms present on apical membranes of distal nephron segments of the mammalian kidney, on basolateral membranes of many non-renal epithelial cells and on certain non-epithelial tissues has been achieved. These transporters represent a major pathway for cellular uptake of chloride critical for chloride absorptive and secretory processes and for cell volume regulation following cell shrinkage. In the mammalian kidney, these sodium-coupled chloride cotransporters represent the major target sites for clinically useful diuretics including the "loop" diuretics [furosemide (Lasix) and bumetanide (Bumex)] and thiazides (such as, chlorothiazide, hydrochlorothiazide and metolazone). Although these Na-(K)-Cl cotransporters exhibit functional and pharmacological differences, they clearly evolved from a common ancestral gene and thus form a new gene family. This information is already advancing our understanding of the evolution, structure and function of these transporters both in renal handling of sodium and in hypertension.
 ...
PMID:The electroneutral Na(+)-(K+)-Cl- cotransport family. 874 68

Studies in rat aorta have shown that the Na-K-2Cl cotransporter NKCC1 is activated by vasoconstrictors and inhibited by nitrovasodilators, contributes to smooth muscle tone in vitro, and is upregulated in hypertension. To determine the role of NKCC1 in systemic vascular resistance and hypertension, blood pressure was measured in rats before and after inhibition of NKCC1 with bumetanide. Intravenous infusion of bumetanide sufficient to yield a free plasma concentration above the IC(50) for NKCC1 produced an immediate drop in blood pressure of 5.2% (P < 0.001). The reduction was not prevented when the renal arteries were clamped, indicating that it was not due to a renal effect of bumetanide. Bumetanide did not alter blood pressure in NKCC1-null mice, demonstrating that it was acting specifically through NKCC1. In third-order mesenteric arteries, bumetanide-inhibitable efflux of (86)Rb was acutely stimulated 133% by phenylephrine, and bumetanide reduced the contractile response to phenylephrine, indicating that NKCC1 influences tone in resistance vessels. The hypotensive effect of bumetanide was proportionately greater in rats made hypertensive by a 7-day infusion of norepinephrine (12.7%, P < 0.001 vs. normotensive rats) but much less so when hypertension was produced by a fixed aortic coarctation (8.0%), again consistent with an effect of bumetanide on resistance vessels rather than other determinants of blood pressure. We conclude that NKCC1 influences blood pressure through effects on smooth muscle tone in resistance vessels and that this effect is augmented in hypertension.
 ...
PMID:Effect of the Na-K-2Cl cotransporter NKCC1 on systemic blood pressure and smooth muscle tone. 1730 11

Bumetanide is a loop diuretic used clinically to treat heart failure, acute renal failure, high blood pressure, and edema. However, diuretics may also be used by athletes as masking agents and to decrease weight. Taken as masking agents, diuretics increase urine production and decrease urinary concentrations of banned performance-enhancing agents, such as anabolic steroids. StarCaps is an over-the-counter dietary supplement marketed as a diet aid. The manufacturer claims that the product contains only natural cleansing agents and emphasizes that it is free from traditional appetite suppressants such as sympathomimetic amines. However, no such disclaimer is made concerning diuretic agents. A single StarCaps capsule was administered to two male and two female volunteers, and their urine specimens were collected at discrete intervals (2, 4, 8, and 12 h) post administration. The specimens were analyzed by a high-performance liquid chromatography-mass spectrometry quadrupole (HPLC-MS) method, and bumetanide was detected in all specimens (4.6 to 351.3 ng/mL). Adjusting the bumetanide concentrations for creatinine content did little to normalize the excretion profiles. Bumetanide was also detected in the StarCaps capsules at concentrations approaching therapeutic doses. HPLC-quadrupole-time-of-flight mass spectrometry was used to confirm the presence of bumetanide in the urine samples and StarCaps capsules. The results showed that unregulated dietary supplements may put consumers at risk for unwitting consumption of prescription medications, and that it is possible for athletes to inadvertently test positive for bumetanide and face disciplinary actions.
 ...
PMID:Detection of bumetanide in an over-the-counter dietary supplement. 1809 21