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)

This double-blind placebo-controlled study was designed to investigate the acute and sustained hormonal, renal hemodynamic, and tubular effects of concomitant ACE and neutral endopeptidase (NEP) inhibition by omapatrilat, a vasopeptidase inhibitor, in men. Thirty-two normotensive subjects were randomized to receive a placebo, omapatrilat (40 or 80 mg), or the fosinopril/hydrochlorothiazide (FOS/HCTZ; 20 and 12.5 mg, respectively) fixed combination for 1 week. Blood pressure, renal hemodynamics, urinary electrolytes and atrial natriuretic peptide excretion, and several components of the renin-angiotensin system were measured for 6 hours on days 1 and 7 of drug administration. When compared with the placebo and the FOS/HCTZ combination, omapatrilat induced a significant decrease in plasma angiotensin II levels (P<0.001 versus placebo; P<0.05 versus FOS/HCTZ) and an increase in urinary atrial natriuretic peptide excretion (P<0.01). These hormonal effects were associated with a significant fall in blood pressure (P<0.01) and a marked renal vasodilatation, but with no significant changes in glomerular filtration rate. The FOS/HCTZ markedly increased urinary sodium excretion (P<0.001). The acute natriuretic response to FOS/HCTZ was significantly greater than that observed with omapatrilat (P<0.01). Over 1 week, however, the cumulative sodium excretion induced by both doses of omapatrilat (P<0.01 versus placebo) was at least as great as that induced by the dose of FOS/HCTZ (P=NS versus FOS/HCTZ). In conclusion, the results of the present study in normal subjects demonstrate that omapatrilat has favorable renal hemodynamic effects. Omapatrilat combines potent ACE inhibition with a sustained natriuresis, which explains its well-documented potent antihypertensive efficacy.
Hypertension 2002 Sep
PMID:Renal hemodynamic and natriuretic effects of concomitant Angiotensin-converting enzyme and neutral endopeptidase inhibition in men. 1221 65

PST 2238 is a new antihypertensive compound that is able to correct the molecular and functional alterations of the renal Na-K pump and the pressor effect associated with either alpha-adducin mutations or high circulating levels of endogenous ouabain (EO) in genetic and experimental rat models. Due to the close relationship between renal Na-K pump function and tubular Na reabsorption, PST 2238 was investigated to determine whether it is endowed with diuretic activity and consequently might trigger alterations of the renin-aldosterone system and the carbohydrate and lipid metabolism often associated with chronic diuretic therapy. In Milan hypertensive (MHS) rats, in which hypertension is genetically associated with alpha-adducin mutation, increased tubular Na reabsorption, and hyperactivation of the renal Na-K pump. PST 2238 reduced blood pressure and normalized the renal Na-K pump activity at oral doses of micro g/kg, but did not induce, either acutely or chronically, any diuretic activity or hormonal or metabolic alterations. In contrast, HCTZ, given to MHS rats orally at 40 mg/kg, although it displayed diuretic activity and reduced the renal Na-K pump activity, did not lower blood pressure and caused hyperactivation of the renin-aldosterone system, hypokaliemia, and hyperglycemia. The findings lead to the conclusion that PST 2238 is a new antihypertensive compound that normalizes the altered function of the renal Na-K pump associated with hypertension in rat models, but that it is devoid of diuretic activity and does not induce the diuretic-associated side effects.
 ...
PMID:PST 2238: a new antihypertensive compound that modulates renal Na-K pump function without diuretic activity in Milan hypertensive rats. 1245 21

This open-label, multicenter, extension study assessed the efficacy and tolerability of telmisartan 80 mg administered alone or with HCTZ and/or other antihypertensive agents over a maximal 1-year treatment period. Of the 690 patients with mild-to-moderate hypertension completing the preceding 6-week, randomized trial (comparing telmisartan 80 mg with losartan 50 mg/HCTZ 12.5 mg combination therapy), 489 patients (70.9%) continued in this extension study. A fixed-titration regimen was employed: all patients received telmisartan 80 mg initially, with the stepwise addition of HCTZ 12.5 mg, HCTZ 25 mg and/or other antihypertensives to attain diastolic blood pressure (DBP) control (<90 mmHg). At the final visit, DBP control was achieved in 70.0% (194/277) of patients maximally titrated to telmisartan 80 mg, 55.8% (48/86) titrated to telmisartan 80 mg + HCTZ 12.5 mg, 54.7% (47/86) titrated to telmisartan 80 mg + HCTZ 25 mg, and 64.7% (22/34) titrated to telmisartan 80 mg + other antihypertensive +/- HCTZ (12.5 or 25 mg). The DBP and systolic blood pressure (SBP) reductions observed in the preceding randomized trial continued during extension treatment. Progressively greater blood pressure reductions occurred with the sequential addition of HCTZ and other antihypertensives. Adding HCTZ 12.5 mg to telmisartan 80 mg was particularly effective at enhancing antihypertensive efficacy. All treatments were well tolerated. Thus, telmisartan 80 mg administered alone or with HCTZ (12.5 or 25 mg) and/or other antihypertensives maintains a clinically significant therapeutic effect over the long term in patients with mild-to-moderate hypertension.
 ...
PMID:Long-term efficacy and tolerability of telmisartan as monotherapy and in combination with other antihypertensive medications. 1245 53

ACE inhibition reduces plasminogen activator inhibitor-1 (PAI-1), a risk factor for myocardial infarction, whereas the effect of angiotensin receptor antagonism on PAI-1 is uncertain. The present study compares the time course of effects of ACE inhibition and angiotensin type 1 (AT1) receptor antagonism on morning plasma PAI-1 antigen. Blood pressure and endocrine, metabolic, and fibrinolytic variables were measured in 20 insulin-resistant (defined by fasting glucose >8.3 mmol/L, body mass index >28 kg/m2, or fasting serum triglyceride > or =2.8 mmol/L) hypertensive subjects (mean age, 47.9+/-2.1 years) (1) before and after 1 week of hydrochlorothiazide 12.5 mg/d, and (2) before and 1, 3, 4, and 6 weeks after addition of ramipril (escalated to 10 mg/d) or losartan (escalated to 100 mg/d). Hydrochlorothiazide decreased systolic (P=0.011) and diastolic (P=0.019) pressure. Ramipril (from 133.6+/-5.1/94.5+/-2.4 to 127.0+/-3.1/91.4+/-3.3 mm Hg) or losartan (from 137.0+/-3.9/93.1+/-2.9 to 123.7+/-2.6/86.4+/-2.1 mm Hg) further reduced systolic (P=0.009) and diastolic (P=0.037) pressure. The pressure effects of the 2 drugs were similar. Hydrochlorothiazide increased plasma PAI-1 (P=0.013) but not tissue-type plasminogen activator (tPA) (P=0.431) antigen. Addition of either ramipril or losartan significantly decreased plasma PAI-1 antigen (P=0.046). However, the effect of losartan on PAI-1 antigen was not sustained throughout the 6-week treatment period, such that there was a significant drugxtime interaction (P=0.043). tPA antigen decreased during either ramipril or losartan (P=0.032), but tPA activity decreased only during losartan (P=0.018). Short-term interruption of the renin-angiotensin-aldosterone system by either ACE inhibition or AT1 receptor antagonism decreases PAI-1 antigen, but the duration of this effect is greater for ACE inhibition than for AT1 receptor antagonism.
Hypertension 2002 Dec
PMID:ACE inhibition versus angiotensin type 1 receptor antagonism: differential effects on PAI-1 over time. 1246 70

1. Hydrochlorothiazide mixture (HCTM) is widely used in China for the treatment of hypertension. This mixture consists of hydrochlorothiazide, triamterene, reserpine, hydralazine and chlordiazpoxide, with small (one-third to one-fifth of normal) doses of each drug. The present study was designed to investigate the effects of this mixture on blood pressure, blood pressure variability (BPV), baroreflex sensitivity (BRS) and end-organ damage in spontaneously hypertensive rats (SHR). 2. The HCTM was mixed in the rat chow and rats were treated for 4 months. After treatment, rats were catheterized and their blood pressure, BPV and BRS were measured in the conscious state. Organ damage was examined after these measurements had been completed. 3. It was found that HCTM not only decreased blood pressure and BPV, but also ameliorated impaired BRS in SHR. The HCTM had an obvious effect on organ protection in SHR. 4. The HCTM prevented left ventricular hypertrophy and this effect was mainly related to a decrease in systolic blood pressure. The effects of HCTM on preventing renal atrophy were mainly determined by BRS. Baroreflex sensitivity was the most important determinant for predicting organ damage in HCTM-treated SHR. 5. In conclusion, long-term treatment of rats with HCTM prevented hypertensive organ damage. Restoration of arterial baroreflex function contributes to organ protection in SHR treated in the long term with HCTM.
 ...
PMID:Restoration of arterial baroreflex function contributes to organ protection in spontaneously hypertensive rats treated with long-term hydrochlorothiazide mixture. 1254 53

Data from the Third National Health and Nutrition Examination Survey (NHANES III) demonstrate that only 11% of people with diabetes who are treated for high blood pressure achieve the blood pressure goal of <130/85 mm Hg recommended in the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). The current study tests the hypothesis that initial therapy with a fixed-dose combination will achieve the recommended blood pressure goal in patients with type 2 diabetes faster than conventional monotherapy. This randomized, double-blind, placebo-controlled study had as a primary end point achievement of blood pressure <130/85 mm Hg. Participants (N=214) with hypertension and type 2 diabetes received either amlodipine/benazepril 5/10 mg (combination) or enalapril 10 mg (conventional) once daily for 4 weeks, titrated to 5/20 mg/day or 20 mg/day, respectively at this time, if target blood pressure was not achieved. Hydrochlorothiazide (HCTZ) 12.5 mg/day was added for the final 4 weeks, if target blood pressure was still not reached. Time from baseline to achieve blood pressure <130/85 mm Hg was shorter in the combination group (5.3+/-3.1 weeks combination vs. 6.4+/-3.8 weeks conventional; p=0.001). At 3 months, more participants in the combination group achieved treatment goal (63% combination vs. 37% conventional; p=0.002). Data analysis at 3 months comparing blood pressure control rates between the fixed-dose combination group (without HCTZ) to the conventional group (receiving HCTZ) showed an even greater disparity in blood pressure goal achievement (87% combination without HCTZ vs. 37% conventional group with HCTZ; p=0.0001). We conclude that initial therapy with a fixed-dose combination may be more efficacious than conventional monotherapy approaches for achieving blood pressure goals in the diabetic patient. A fixed-dose combination approach appears as safe as the current conventional approaches.
 ...
PMID:Achieving goal blood pressure in patients with type 2 diabetes: conventional versus fixed-dose combination approaches. 1282 83

It is not clear which duration of treatment is needed to achieve complete efficacy with fixed low dose antihypertensive therapy. The aim of this study was to compare blood pressure control rate in patients treated with bisoprolol 2.5 mg/HCTZ 6.25 mg, not controlled after 4 weeks, but treated at the same dosage for one more month to patients not controlled after 4 weeks, and uptitrated to bisoprolol 5 mg/HCTZ 6.25 mg for one month. The 641 patients who entered the study had a mean age of 58 +/- 12 with SBP/DBP at baseline of 165 +/- 12/96 +/- 7 mmHg. After 4 weeks, 252 (39%) where normalized (< 140/90) with SBP/DBP reductions of -27/-15 mmHg. In uncontrolled patients, 19% of those randomized to B 2.5 mg/H 6.25 mg and 33% of those treated with B 5 mg/H 6.25 mg where normalized at the end of the study (p < 0.001). Multivariate analysis indicates determinants of blood pressure normalisation after 4 weeks with B2.5 mg/HCTZ 6.25 mg as female gender, initial BP < 175/105 mmHg, previously untreated hypertension, age < 50 years. In conclusion, when the initial therapy with bisoprolol 2.5 mg/HCTZ 6.25 mg is not sufficient to control blood pressure, continuation with the same dosage 4 weeks longer increases the rate of blood pressure control. However, up-titration to bisoprolol 5 mg/6.25 mg is more efficacious to increase the number of patients with a final blood pressure < 140/90 mmHg.
 ...
PMID:[Factors predicting blood pressure normalization in hypertensive patients treated with a fixed-dose combination of bisoprolol 2.5 mg/hydrochlorothiazide/6.25 mg]. 1294 22

Kinzalkomb marketed in Belgium by Bayer is a fixed combination of telmisartan 80 mg and hydrochlorothiazide 125 mg for the treatment of hypertension. New guidelines for the treatment of hypertension were recently released both in Europe and the United States (see article by J.M. Krzesinski in this issue). They offer the choice of using a fixed biotherapy even as first line treatment. Hydrochlorothiazide at low dose is a frequent component of such biotherapies: it is efficacious and secure. Telmisartan is a highly selective blocker of angiotensin II AT1 receptors ("sartans"); it is at least as effective as the classical antihypertensive agents; thanks to its half-life, the longest of all sartans', it provides adequate antihypertensive coverage throughout the whole 24-hour postdose interval and particularly over the last 6 hours of the dosage interval. Its tolerability profile is equivalent to placebo. The combination telmisartan-hydrochlorothiazide is more effective than each agent alone at lowering blood pressure; furthermore telmisartan possesses a potassium-sparing effect that when the two drugs are coadministered attenuates the kaliuretic effect of hydrochlorothiazide. Various large trials are currently under way (ONTARGET, TRANSCEND, PROFESS, PROTECTION, DETAIL). These studies which together involve some 50,000 patients will hopefully help to further specify the role of telmisartan in condition which require an intervention on the renin-angiotensin system.
 ...
PMID:[Kinzalkomb, a fixed telmisartan-hydrochlorothiazide combination for the treatment of hypertension]. 1462 54

Thiazide diuretics are one of the preferred pharmacologic treatments for hypertension. Hydrochlorothiazide and chlorthalidone have been the 2 most commonly used diuretics in major clinical trials. Treatment guidelines and compendia often consider these 2 drugs interchangeable agents within the class of thiazide or thiazide-like diuretics. Many sources list them as equipotent. Despite these beliefs, there is some suggestion that cardiovascular outcomes are not necessarily the same with these 2 drugs. We conducted a literature search from 1960 to 2003 to identify studies that evaluated the pharmacokinetic and blood pressure-lowering effects of these 2 agents. There are significant pharmacokinetic and pharmacodynamic differences between these diuretics. Chlorthalidone is approximately 1.5 to 2.0 times as potent as hydrochlorothiazide, and the former has a much longer duration of action. Whether these pharmacokinetic and pharmacodynamic features cause differences in outcomes is not known.
Hypertension 2004 Jan
PMID:Hydrochlorothiazide versus chlorthalidone: evidence supporting their interchangeability. 1463 21

Hydrochlorothiazide and other thiazide-like diuretics are considered as a first-line drug for initial therapy in uncomplicated arterial hypertension [1]. There are several reports [2-6] of thiazide-induced cholecystitis, but here we report a case of serious hepatotoxicity associated with hydrochlorothiazide treatment.
 ...
PMID:Hydrochlorothiazide induced hepato-cholestatic liver injury. 1527 38


<< Previous 1 2 3 4 5 6 7 8 9 10