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PubMed2004

Effects of indapamide, a thiazide-like diuretic, on structure of cerebral arterioles in hypertensive rats.

We examined the effects of indapamide, a thiazide-like diuretic, on cerebral arterioles in spontaneously hypertensive rats (SHR). The structure and mechanics of cerebral arterioles were examined in untreated Wistar Kyoto rats (WKY) and SHR that were untreated or treated for 3 months with a low (1 mg/kg per day) or a high (10 mg/kg per day) dose of indapamide. We measured pressure, diameter, and cross-sectional area of the vessel wall (CSA) in maximally-dilated (EDTA) cerebral arterioles. Treatment of SHR with the high dose of indapamide normalized cerebral arteriolar mean pressure (62+/-4 [mean+/-SEM] versus 59+/-3 mm Hg in WKY and 88+/-6 mm Hg in untreated SHR; P<0.05), pulse pressure (13+/-1 versus 10+/-1 mm Hg in WKY and 20+/-1 mm Hg in untreated SHR; P<0.05), and CSA (1080+/-91 versus 1100+/-48 microm2 in WKY and 1439+/-40 microm2 in untreated SHR; P<0.05). In contrast, treatment of SHR with the low dose of indapamide did not normalize arteriolar mean (72+/-3) and pulse pressure (20+/-1 mm Hg), but did normalize CSA (1091+/-52 microm2). Treatment with either dose of indapamide failed to increase external diameter in cerebral arterioles of SHR (89+/-4 and 92+/-4 microm, respectively, versus 103+/-6 microm in WKY and 87+/-4 microm in untreated SHR). Finally, treatment with indapamide attenuated the rightward shift of the stress-strain curve in SHR, suggesting that treatment with indapamide attenuated increases in distensibility of cerebral arterioles in SHR. These findings suggest that, whereas thiazide-like diuretics may not attenuate eutrophic inward remodeling of cerebral arterioles in SHR, they may attenuate hypertrophic inward remodeling via a mechanism unrelated to their pressor effects.

Animals↗
PubMed1988

Volume (weight) loss and blood pressure response following thiazide diuretics.

Correlations were made between weight change (as an index of volume loss) and blood pressure (BP) reduction before and after hydrochlorothiazide treatment. A total of 343 patients with mild to moderate hypertension (95-114 mm Hg) received hydrochlorothiazide alone. The diuretic was titrated from 50 to 100 to 200 mg daily as needed until the diastolic BP fell below 90 mm Hg (goal BP) or side effects supervened. Of the 305 patients who completed the 10-week titration period, 65% attained goal BP. The effective dose of hydrochlorothiazide in 52% of these responders was 50 mg/day, and this was associated with weight loss averaging 1.58 kg. An additional 29% achieved goal BP with a similar degree of weight loss, but they required double the dose, or 100 mg/day. The remaining 19% of responders required significantly greater weight reductions averaging 3.14 kg to achieve goal BP, which necessitated hydrochlorothiazide, 200 mg/day. More blacks than whites attained goal BP despite similar degrees of weight loss in the two races. Plasma renin activity was initially higher in whites than in blacks and rose significantly more in blacks and whites requiring the greatest volume losses and the highest dose of hydrochlorothiazide to attain goal BP. Nonresponders had less weight loss than responders. Thus, diuretic dose requirements vary in different patients and are related either to different volume losses in response to a given dose or to different degrees of BP reduction in response to the same volume loss.

Black People↗
PubMed1994

Glucose and insulin levels during diuretic therapy in hypertensive men.

We investigated serum glucose and insulin levels resulting from thiazide or thiazide-like diuretic administration and determined whether they were associated with serum or intracellular potassium or magnesium values. We also explored the role of obesity both alone and with thiazides on serum insulin and glucose. Hypertensive men were withdrawn from diuretics and repleted with oral potassium and magnesium and then randomized to 2 months of treatment with (1) hydrochlorothiazide, (2) hydrochlorothiazide with oral potassium, (3) hydrochlorothiazide with oral potassium and magnesium (4) hydrochlorothiazide and triamterene, (5) chlorthalidone, or (6) placebo. Serum was available from 202 participants for insulin and glucose determinations. Mean fasting serum glucose and insulin did not change significantly after 2 months of randomized therapy with the exception of participants randomized to chlorthalidone, who had significant increases in both serum insulin and glucose (P < .05 and P < .01, respectively). As body mass index increased, there was a corresponding increase in serum insulin and to a lesser degree in serum glucose. Also, as body mass index increased, participants taking hydrochlorothiazide had a corresponding increase of serum insulin (P < .05). After treatment, intracellular potassium and magnesium were both associated with higher serum insulin (P < .001 for each), and serum potassium was associated with higher and serum magnesium with lower serum glucose (P < .01 for each). In most hypertensive men, treatment with 50 mg chlorthalidone increases glucose and insulin levels, whereas administration of 50 mg hydrochlorothiazide, with or without potassium and/or magnesium conserving strategies, does not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2001

C825T polymorphism of the G protein beta(3)-subunit and antihypertensive response to a thiazide diuretic.

The T allele of the C825T polymorphism of the gene encoding the beta(3)-subunit of G proteins has been associated with increased sodium-hydrogen exchange and low renin in patients with essential hypertension. To assess its association with blood pressure response to diuretic therapy, we measured the C825T polymorphism in 197 blacks (134 men, 63 women) and 190 non-Hispanic whites (76 men, 114 women) with essential hypertension (mean+/-SD age 48+/-7 years), who underwent monotherapy with hydrochlorothiazide for 4 weeks. Mean declines in systolic and diastolic blood pressures were 6+/-2 (P:<0.001) and 5+/-1 (P:<0.001) mm Hg greater, respectively, in TT than in CC homozygotes. Responses in heterozygotes were intermediate between the homozygous groups. Other univariate predictors of greater blood pressure responses included black race, female gender, higher pretreatment blood pressure, older age, lower waist-to-hip ratio, and measures of lower renin-angiotensin-aldosterone system activity. After the effects of the other predictors were considered, the TT genotype remained a significant predictor of greater declines in systolic and diastolic blood pressures. Thus, the C825T polymorphism of the G protein beta(3)-subunit may help identify patients with essential hypertension who are more responsive to diuretic therapy.

Adult↗
PubMed2006

Role of diuretics in the prevention of heart failure: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial.

BACKGROUND: Hypertension is a major cause of heart failure (HF) and is antecedent in 91% of cases. The Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) stipulated assessment of the relative effect of chlorthalidone, lisinopril, and amlodipine in preventing HF. METHODS AND RESULTS: ALLHAT was a double-blind, randomized, clinical trial in 33,357 high-risk hypertensive patients aged > or =55 years. Hospitalized/fatal HF outcomes were examined with proportional-hazards models. Relative risks (95% confidence intervals; P values) of amlodipine or lisinopril versus chlorthalidone were 1.35 (1.21 to 1.50; <0.001) and 1.11 (0.99 to 1.24; 0.09). The proportional hazards assumption of constant relative risk over time was not valid. A more appropriate model showed relative risks of amlodipine or lisinopril versus chlorthalidone during year 1 were 2.22 (1.69 to 2.91; <0.001) and 2.08 (1.58 to 2.74; <0.001), and after year 1, 1.22 (1.08 to 1.38; P=0.001) and 0.96 (0.85 to 1.10; 0.58). There was no significant interaction between prior medication use and treatment. Baseline blood pressures were equivalent (146/84 mm Hg) and at year 1 were 137/79, 139/79, and 140/80 mm Hg in those given chlorthalidone, amlodipine, and lisinopril. At 1 year, use of added open-label atenolol, diuretics, angiotensin-converting enzyme inhibitors, and calcium channel blockers in the treatment groups was similar. CONCLUSIONS: HF risk decreased with chlorthalidone versus amlodipine or lisinopril use during year 1. Subsequently, risk for those individuals taking chlorthalidone versus amlodipine remained decreased but less so, whereas it was equivalent to those given lisinopril. Prior medication use, follow-up blood pressures, and concomitant medications are unlikely to explain most of the HF differences. Diuretics are superior to calcium channel blockers and, at least in the short term, angiotensin-converting enzyme inhibitors in preventing HF in hypertensive individuals.

Adrenergic beta-Antagonists↗
PubMed1993

Effect of thiazide diuretics against neurally mediated contraction of guinea pig airways. Contribution of carbonic anhydrase.

The effect of thiazide diuretics on neurally and agonist-induced contractile responses of guinea pig airways in vitro were investigated. Tracheal or bronchial strips were suspended in organ baths and isometric tension recorded. Chlorothiazide (CTZ, 10(-4) to 3 x 10(-3) M), hydrochlorothiazide (HCTZ, 10(-3) M), and dichlorphenamide (DCPM, 10(-3) M) significantly potentiated contraction of tracheal strips induced by electrical field stimulation (EFS). They also increased acetylcholine (ACh)- but not carbachol-induced tracheal contraction. In the presence of atropine and propranolol, on the other hand, CTZ and DCPM but not HCTZ significantly inhibited EFS-induced contraction in bronchial strips. We determined whether carbonic anhydrase inhibition could mimic the effects of CTZ and DCPM. Acetazolamide (ATZ), an inhibitor of carbonic anhydrase, had no effect on either EFS- or ACh-induced contraction in tracheal strips but significantly inhibited nonadrenergic, noncholinergic (NANC) contractile responses induced by EFS in bronchial strips. CTZ, DCPM, and ATZ did not affect substance P-induced contractile responses in the bronchi. We conclude that CTZ, DCPM, and ATZ attenuate NANC neurally mediated bronchial contraction by preventing the release of contractile neuropeptides from sensory nerve endings. This effect may occur through inhibition of carbonic anhydrase activity. In addition, thiazide diuretics potentiate contractile responses to ACh in the trachea, probably through inhibition of acetylcholinesterase activity.

Acetylcholine↗
PubMed1985

Depression after treatment with thiazide diuretics for hypertension.

The authors reports eight cases of depression induced by thiazide diuretics prescribed for hypertension and discusses possible mechanisms behind this action. The side effects of thiazide diuretics may be overlooked when they are used with other hypertensives known to cause depression.

Adult↗
PubMed1994

Antihypertensive drugs and glucose metabolism: a comparison between a diuretic and felodipine, a new calcium antagonist, when added to a beta-blocker in non-diabetic hypertensive women.

Felodipine, a vascular selective antihypertensive calcium antagonist, was compared with hydrochlorothiazide, a diuretic, with respect to glucose tolerance. An open crossover study was performed comprising 16 non-diabetic hypertensive women (age range 59-75 years). The women continued to take a beta-blocker as a basal therapy. Each treatment period lasted three months. The blood pressure was similar irrespective of treatment. Blood glucose values were not significantly different during the oral glucose tolerance test. Serum insulin levels after glucose administration were lower when the patients were treated with felodipine than when taking hydrochlorothiazide. A possible explanation for this observation may be an increased insulin release as a consequence of treatment with a diuretic in order to maintain normal blood glucose levels during the glucose tolerance test. Felodipine appears preferable to hydrochlorothiazide as an addition to a beta blocker in hypertensive patients from a glucose metabolism point of view.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Insensitivity of the chicken embryo to the ototoxicity of aminoglycoside antibiotics and a loop diuretic.

Guinea pigs are routinely used in the histological evaluation of the cochlea as a method of testing for ototoxicity, but the procedures are very time-consuming. Because the avian cochlea is easier to examine and newly hatched chicks are sensitive to the ototoxic effects of gentamicin, birds may be useful in testing for ototoxicity. The use of chicken embryos would be even better for testing, but whether or not chicken embryos are sensitive to ototoxicants is unknown. In an attempt to determine whether or not chicken embryos may be used instead of guinea pigs in screening tests for ototoxicity, aminoglycoside antibiotics and a loop diuretic, ethacrynic acid, were administered to chicken embryos. A maximum-tolerated dose of gentamicin, kanamycin, streptomycin, ethacrynic acid, or a combination of gentamicin and ethacrynic acid was administered to fertile eggs of White Leghorn chickens on incubation days 10-17. To compare the effect of route of exposure on ototoxicity, gentamicin was administered by injection into the allantoic space, yolk sac, and air cell as well as by submerging the egg in gentamicin solution. With the preferred air cell route the effects of the ototoxic drugs kanamycin, streptomycin, ethacrynic acid, and a combination of ethacrynic acid and gentamicin were compared. On incubation day 18, cochleas were removed from the chicken embryos. Serial sections of these avian cochleas were examined and hair cells were counted. No significant difference was seen between the number of hair cells in cochleas of control chicken embryos and those from chicken embryos treated with drugs. Therefore, the chicken embryo appears to be insensitive to the ototoxicity of aminoglycoside antibiotics and a loop diuretic.

Animals↗
PubMed1993

Diuretic and diet effect on Menière's disease evaluated by the 1985 Committee on Hearing and Equilibrium guidelines.

Fifty-four patients, diagnosed with Menière's disease and treated with diuretics and a low-salt diet, were evaluated retrospectively with the 1985 AAO/HNS Committee on Hearing and Equilibrium (CHE) guidelines for vertigo and hearing changes. The patient data base was also evaluated with other methods that helped determine the effectiveness of the 1985 AAO/HNS CHE guidelines. After 24 months of therapy, vertigo control was complete or substantial in 79% of the patients, limited or insignificant in 19%, and worse in 2% as evaluated by the CHE 1985 guidelines. Hearing improved in 35% of the patients, was unchanged in 29%, was worse in 22%, and could not be classified by CHE guidelines in 14%. Hearing was also evaluated by comparison of individual thresholds before medical therapy, and at 22 and 74 months after the start of medical therapy. We found a stabilization of low- and mid-threshold frequencies, with an average rate of hearing loss approximating 0 dB/yr with 74 months of followup. The results of this preliminary study suggest that diuretics and a low-salt diet may decrease the natural progression of sensorineural hearing loss in patients with Menière's disease. Compared with other methods of data analysis, the 1985 CHE guidelines lacked sensitivity to evaluate the hearing changes observed.

Academies and Institutes↗
PubMed1980

Diuretic urography in the assessment of obstruction of the pelvi-ureteric junction.

Twenty adult patients with urographic evidence of unilateral, moderately wide renal pelves were examined by routine and diuretic urography. Planimetry of the corresponding calyx system of the two examinations was performed. An increase in size by more than 20 per cent following osmotic diuresis indicated an obstruction of the pelvi-ureteric junction in kidneys with moderately wide renal pelves. Diuretic urography may be useful to diagnose obstruction as a cause of moderately wide renal pelves and to assess operative results.

Adult↗
PubMed2004

Prevention of acute renal failure: role of vaso-active drugs, mannitol and diuretics.

Evidence exists that acute renal failure (ARF) independently increases mortality risk in critically-ill patients. Therefore prevention of ARF seems of paramount importance. Preservation of renal blood flow and (sufficient) perfusion pressure favourably influences the prevention of renal function deterioration in the critically-ill septic patient. The first step to achieve this is infusion of fluids, either crystalloids or colloids, with the aim of optimal fluid resuscitation. Although "optimal fluid resuscitation" is poorly defined, in clinical practice it can be considered as the point where a certain preload is obtained, after which no further increase of cardiac output is observed with further fluid infusion. Vasoactive drugs can be added to this regimen in case of insufficient restoration of flow and especially perfusion pressure. The addition of norepinephrine can be of value if high doses of dopamine fail to restore perfusion pressure. No evidence exists that low-dose dopamine prevents renal failure and, therefore, dopamine should not be given for this indication. The use of diuretic agents can be harmful, as indicated by observational and cohort studies. Although mannitol flushes out intratubular casts and increases tubular flow, which is favorable in myoglobinuria or hemoglobinuria, so far no well designed clinical studies have demonstrated its efficacy in ARF In conclusion, there is currently no convincing evidence for any benefit from diuretic agents and/or (low dose) dopamine in the prevention of ARF. High quality intensive care and avoidance of harm is, therefore, the current standard of the prevention of ARF.

Acute Kidney Injury↗
PubMed1984

Cardiovascular toxicity of diuretics related to magnesium depletion.

The chronic administration of common loop or distal tubular diuretics may lead to somatic depletion of Mg2+. The resultant deficiency of this cation causes an increase in intramyocardial cytosolic Ca2+ and aggravates the decrease in intramyocardial K+ provoked by diuretics through their hyperkaliuretic effect. Thus the myocardium is electrically destabilized and cardiac arrhythmias may develop. Mg2+ deficiency positively contributes to the development of atherogenic alterations in lipid metabolism, vasospastic phenomena in the coronary and cerebrovascular territories, myocardial infarction and to the retardation of infarct healing and the occurrence of ventricular arrhythmias during the acute phase of infarction.

Arrhythmias, Cardiac↗
PubMed1981

Potentiation of myelosuppression from cancer chemotherapy and thiazide diuretics.

Fourteen patients with metastatic breast cancer and concomitant essential hypertension received treatment with combination chemotherapy (cyclophosphamide, methotrexate, and 5-fluorouracil) and thiazide diuretics. Significant augmentation of granulocytopenia during thiazide-chemotherapy combination, as compared with chemotherapy without thiazides, was observed in all patients. The most consistent changes in the neutrophil count were observed during the period of maximal myelosuppression from the antitumor drugs. An interaction between the thiazide diuretic and one or more of the cytotoxic agents is a possible explanation for the findings. The implications of this phenomenon are discussed.

Antineoplastic Agents↗
PubMed1977

Pharmacology of Bay g 2821, a long-acting, high-ceiling diuretic.

Bay g 2821 is a diuretic, from a new class of chemical substances, with both the efficacy of diuretics with a high-ceiling activity, such as furosemide, bumetanide and ethacrynic acid, and the prolonged duration of action of thiazides. Pharmacological investigations showed that Bay g 2821 was more potent than furosemide in dogs but less potent in rats. Bay g 2821 did not differ from furosemide in excretion of electrolytes. Further studies showed that Bay g 2821 had an antihypertensive effect in dogs, spontaneously hpertensive rats, and in rats with artificially-induced renal hypertension. Other pharmacological studies did not reveal any other significant effects.

Animals↗
PubMed1977

Diuretic effects of Bay g 2821 in patients with advanced renal failure.

Clearance studies were carried out in 18 non-oedematous patients with advanced renal failure (glomerular filtration rate less than 12 ml/min) to assess the diuretic effects of Bay g 2821 given different oral doses (120 mg to 360 mg). The results showed a significant increase in urinary volume and in clearances of sodium, calcium, magnesium, chloride, inorganic phosphorus and 51CrEDTA. There were no significant changes, however, in clearance of PAH, urea and uric acid. The diuretic response started in the first hour after drug intake, reached a maximum after 3 to 5 hours, and declined slowly in the following 3 to 4 hours. In patients with a glomerular filtration rate less than 3 ml/min the drug lost its effect. In rates between 5 to 10 ml/min the efficacy of Bay g 2821 was comparable to that of furosemide and ethacrynic acid. No side-effects were reported.

Diuretics↗
PubMed1978

Diuretic effect of a combined preparation of frusemide and slow-release potassium chloride.

An open randomized crossover study was carried out in 10 healthy volunteers to compare the diuretic effect of a single tablet combining 40 mg frusemide and a slow-release formulation of 600 mg potassium chloride with that of the two agents given in separate tablets. The results showed that both treatments had a similar effect on urinary volume and on sodium and potassium excretion, but the hourly urinary volumes during the first 6 hours suggested that the diuretic action of the combined formulation occurred slightly earlier after administration.

Adult↗
PubMed1980

Combined antihypertensive therapy: vasodilatation using prazosin in combination with beta-adrenoceptor blockers and diuretics.

An open study was carried out in 20 hypertensive patients, who had inadequate blood pressure control with beta-adrenoceptor blocking drugs and diuretics, to investigate the effects of adding prazosin to their existing treatment regimen. Patients received a mean daily dose of prazosin of 8.7 +/- 4.4 mg over a period of 12 weeks. The results showed that there was a significant reduction in systolic and diastolic blood pressures in the resting position. Only a few side-effects were reported and these occurred during the first 4 weeks whilst prazosin dosage was being adjusted. Weight increase, however, was noted in all but 4 of the patients. It is suggested that this may have been due partly to fluid retention, even though the majority were receiving diuretics, or possibly to changed carbohydrate-insulin metabolism.

Adrenergic beta-Antagonists↗