benazepril and Hypertension--Renal

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Pressure; Clinical Trials as Topic; Diagnosis, Differential; Humans; Hypertension, Renal; Natriuresis; Renin-Angiotensin System; Sodium, Dietary; Vascular Resistance

Angiotensin II (AII) is the well-known determinant of kidney damage increasing intraglomerular pressure, matrix expansion and fibroblast proliferation. Renin-angiotensin system (RAS) inhibition, limiting the hemodynamic effects of AII, reduces proteinuria and is renoprotective in the long term.. We studied 15 chronic proteinuric patients by Doppler ultrasonography to clarify the intrarenal hemodynamic changes during RAS blockade by Benazepril (10-20 mg/day) alone and combined with Valsartan (80-160 mg/day). We also investigated the correlation between hemodynamic indices, RAS components and antiproteinuric effect.. After 1 month of Benazepril proteinuria, resistive index (RI) and pulsatility index (PI) significantly decreased and proteinuria reduction was directly correlated to decrease in RI (r = 0.55, p = 0.03). Contrarily, after 1 month of combined therapy, RI and PI restored to baseline and progressively increased in the following 3 months, while proteinuria decreased. Increase in RI was directly correlated to concomitant increase in plasma renin activity (r = 0.65, p = 0.01) suggesting a direct role of renin in restoring intrarenal resistances.. The hemodynamic changes caused by RAS inhibitors partially contribute to the antiproteinuric effect. Other RAS components, such as renin, may contribute to renal vasoconstriction and could be a further determinant of kidney damage besides a promising target for renoprotection.

Topics: Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Female; Humans; Hypertension, Renal; Male; Middle Aged; Proteinuria; Renal Circulation; Renin; Renin-Angiotensin System; Tetrazoles; Treatment Outcome; Valine; Valsartan

The Renoprotection of Optimal Antiproteinuric Doses (ROAD) study was performed to determine whether titration of benazepril or losartan to optimal antiproteinuric doses would safely improve the renal outcome in chronic renal insufficiency. A total of 360 patients who did not have diabetes and had proteinuria and chronic renal insufficiency were randomly assigned to four groups. Patients received open-label treatment with a conventional dosage of benazepril (10 mg/d), individual uptitration of benazepril (median 20 mg/d; range 10 to 40), a conventional dosage of losartan (50 mg/d), or individual uptitration of losartan (median 100 mg/d; range 50 to 200). Uptitration was performed to optimal antiproteinuric and tolerated dosages, and then these dosages were maintained. Median follow-up was 3.7 yr. The primary end point was time to the composite of a doubling of the serum creatinine, ESRD, or death. Secondary end points included changes in the level of proteinuria and the rate of progression of renal disease. Compared with the conventional dosages, optimal antiproteinuric dosages of benazepril and losartan that were achieved through uptitration were associated with a 51 and 53% reduction in the risk for the primary end point (P = 0.028 and 0.022, respectively). Optimal antiproteinuric dosages of benazepril and losartan, at comparable BP control, achieved a greater reduction in both proteinuria and the rate of decline in renal function compared with their conventional dosages. There was no significant difference for the overall incidence of major adverse events between groups that were given conventional and optimal dosages in both arms. It is concluded that uptitration of benazepril or losartan against proteinuria conferred further benefit on renal outcome in patients who did not have diabetes and had proteinuria and renal insufficiency.

Topics: Adult; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Dose-Response Relationship, Drug; Female; Humans; Hypertension, Renal; Losartan; Male; Middle Aged; Proteinuria; Renal Insufficiency, Chronic; Treatment Outcome

The aim of this study was to compare the effects of an angiotensin-converting enzyme (ACE) inhibitor and alphabeta blocker in combination with a calcium antagonist on the progression of renal function and left ventricular hypertrophy (LVH) in patients with chronic renal insufficiency and hypertension. The 65 subjects in this study were recruited from a cohort of 316 patients. The main criteria for inclusion were echocardiographic diagnosis of LVH (posterior wall thickness >12 mm) and serum creatinine of more than 1.5 mg/dl. Antihypertensive treatments were switched to the combination of amlodipine at a dose of 5 mg and benazepril at a dose of 2.5 mg daily or the combination of amlodipine at a dose of 5 mg and arotinolol at a dose of 20 mg daily at random irrespective of whether or not patients had been previously treated. The follow-up period was 2 years. Systolic and diastolic blood pressure were significantly reduced from 150/90 +/- 15/11 mmHg to 130/75 +/- 11/9 mmHg (ACE) and the levels of serum creatinine were increased significantly from 1.8 +/- 0.3 to 2.0 +/- 0.4 mg/dl (ACE). In the alphabeta-blocker group, these two values were similar and no significant changes were found. PWT was decreased from 14.2 +/- 0.6 to 12.9 +/- 0.3 cm in alphabeta blocker but was not significantly decreased in the ACE inhibitor group. In conclusion, combination therapy with a calcium antagonist and abeta blocker might be effective treatment for hypertensive patients with chronic renal insufficiency and left ventricular hypertrophy.

Topics: Adrenergic alpha-Antagonists; Adrenergic beta-Antagonists; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Cohort Studies; Creatinine; Drug Therapy, Combination; Echocardiography; Female; Follow-Up Studies; Humans; Hypertension, Renal; Hypertrophy, Left Ventricular; Kidney Failure, Chronic; Male; Middle Aged; Pilot Projects; Propanolamines; Proteinuria

This study investigated the effects of benazepril administered in the morning or evening on the diurnal variation of renin-angiotensin-aldosterone system (RAAS) and clock genes in the kidney. The male Wistar rat models of 5/6 subtotal nephrectomy (STNx) were established. Animals were randomly divided into 4 groups: sham STNx group (control), STNx group, morning benazepril group (MB) and evening benazepril group (EB). Benazepril was intragastrically administered at a dose of 10 mg/kg/day at 07:00 and 19:00 in the MB group and EB group respectively for 12 weeks. All the animals were synchronized to the light:dark cycle of 12:12 for 12 weeks. Systolic blood pressure (SBP), 24-h urinary protein excretion and renal function were measured at 11 weeks. Blood samples and kidneys were collected every 4 h throughout a day to detect the expression pattern of renin activity (RA), angiotensin II (AngII) and aldosterone (Ald) by radioimmunoassay (RIA) and the mRNA expression profile of clock genes (bmal1, dbp and per2) by real-time PCR at 12 weeks. Our results showed that no significant differences were noted in the SBP, 24-h urine protein excretion and renal function between the MB and EB groups. There were no significant differences in average Ald and RA content of a day between the MB group and EB group. The expression peak of bmal1 mRNA was phase-delayed by 4 to 8 h, and the diurnal variation of per2 and dbp mRNA diminished in the MB and EB groups compared with the control and STNx groups. It was concluded when the similar SBP reduction, RAAS inhibition and clock gene profile were achieved with optimal dose of benazepril, morning versus evening dosing of benazepril has the same renoprotection effects.

Topics: Animals; Antihypertensive Agents; Benzazepines; Circadian Rhythm; CLOCK Proteins; Drug Chronotherapy; Gene Expression Profiling; Hypertension, Renal; Kidney; Male; Nephrectomy; Rats; Rats, Wistar; Renin-Angiotensin System; Treatment Outcome

To determine effects of the angiotensin converting enzyme inhibitor benazepril in cats with induced renal insufficiency.. 32 cats.. Renal mass was surgically reduced, and cats were assigned to 1 of 4 eight-cat groups. Group 1 received placebo, whereas groups 2, 3, and 4 received benazepril hydrochloride orally once daily for approximately 6.5 months at the following doses: group 2, 0.25 to 0.50 mg/kg of body weight; group 3, 0.50 to 1.00 mg/kg; and group 4, 1.00 to 2.00 mg/kg. Arterial blood pressures, glomerular filtration rate (GFR), and renal plasma flow were determined before treatment and during the treatment period. Other determinants of renal hemodynamics were measured by use of micropuncture techniques. Renal biopsy specimens were examined microscopically.. Compared with cats that received placebo, mean systolic arterial blood pressure was significantly less and GFR significantly greater in cats that received benazepril. Glomerular capillary pressure and the ratio of efferent to afferent arteriolar vascular resistance were also significantly less in treated cats. However, histologic differences in renal specimens were not detected.. Treatment with benazepril sustained single nephron GFR in remnant nephrons of cats with induced renal insufficiency. Administration of benazepril was also associated with a small but significant reduction in degree of systemic hypertension and an increase in whole kidney GFR. Benazepril may be an effective treatment to slow the rate of progression of renal failure in cats with renal disease.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Blood Pressure; Blood Urea Nitrogen; Cat Diseases; Cats; Creatinine; Echocardiography; Female; Glomerular Filtration Rate; Heart Rate; Hypertension, Renal; Kidney Diseases; Male; Random Allocation; Renal Plasma Flow; Telemetry

To explore the influence of angiotensin-converting enzyme inhibitors (ACEI) on plasma endothelin (ET-1), nitric oxide (NO) and renal function in renal-hypertension patients.. Sixty renal-hypertension patients (Group II) were treated with ACEI (lotensin) for 10 weeks then we measure their blood pressure (BP), plasma ET-1, NO and renal functions (BUN, Scr and proteinuria) before and after the treatment. Thirty healthy persons (Group I) acted as control.. The level of plasma ET-1 was higher and plasma NO was lower in Group II than those in Group I. After the treatment of ACEI plasma ET-1 and proteinuria were decreased (P < 0.01), and NO increased in Group II significantly (P < 0.01), while BUN and Scr decreased in abnormal-renal function patients (Group II2) (P < 0.05, P < 0.01).. The Study indicates that: ACEI is effective to renal hypertension; it decreases plasma ET-1 and increases NO in the renal hypertension patients; ACEI may play an important role in protection of renal functions and prolonging the chronic renal failure.

Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Urea Nitrogen; Endothelin-1; Female; Humans; Hypertension, Renal; Kidney Function Tests; Male; Middle Aged; Nitric Oxide

This study tested whether the angiotensin-converting enzyme inhibitor (ACEI) benazepril can improve the insulin resistance and glucose tolerance in uremia. Fifteen uremic hypertensive patients were treated with benazepril in a dose of 10-20 mg per day for ten weeks, and ten healthy subjects, matched in age, sex ratio and body mass index (BMI), served as the control group. Before and after the treatment, an oral 75 g glucose tolerance test (OGTT) and insulin release test (IRT) were performed in two groups above, and the blood glucose and serum insulin concentrations at 0, 60, 120 and 180 minutes after glucose load were examined, and the insulin glycoregulatory activity, including insulin sensitivity index (ISI), glucose uptake rate (M), total areas under the glucose and insulin curves during OGTTs (AUCG AUCINS), was calculated. The changes of serum potassium and renal function before and after treatment were observed. It showed that (1) benazepril could reduce blood pressure significantly (SBP decreased from 174.8 +/- 12.0 mmHg to 151.5 +/- 9.0 mmHg, p <0.001; DBP decreased from 108.0 +/- 8.2 mmHg to 95.3 +/- 9.0 mmHg, p <0.001). The total response rate was 86.7%. (2) After treatment with benazepril for ten weeks, the blood glucose and serum insulin concentrations after glucose load and AUCG, AUCINS values in the uremic patients were significantly lower than before treatment, but were still significantly higher than in the controls. The values of ISI and M in the uremic patients after treatment were much higher than before treatment, but were still significantly lower than in the control subjects. (3) The differences of serum potassium and creatinine levels before and after treatment were not significant. These findings indicate that benazepril can not only reduce blood pressure effectively and safely, but also partly improve insulin resistance, hyperinsulinemia and glucose intolerance in uremia.

Topics: Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Case-Control Studies; Female; Glucose Intolerance; Humans; Hyperinsulinism; Hypertension, Renal; Insulin Resistance; Male; Middle Aged; Treatment Outcome; Uremia

Cardiac hypertrophy is associated with altered Ca2+ handling and may predispose to the development of LV dysfunction and cardiac failure. At the cellular level, the re-expression of ANF represents a well-established marker of myocyte hypertrophy while the decreased expression of the sarcoplasmatic reticulum (SR) Ca(2+)-ATPase is thought o play a crucial role in the alterations of Ca2+ handling and LV function. We assessed the dose-dependent effect of chronic ACE inhibition or AT1 receptor blockade on cardiac function in relation to the cardiac expression of the SR Ca(2+)-ATPase and ANF.. Renal hypertensive rats (2K-1C) were treated for 12 weeks with three different doses of the ACE inhibitor benazepril, the AT1-receptor antagonist valsartan (each drug 0.3, 3, and 10 mg/kg per day i.p.) or placebo. LV dimensions, hypertrophy and wall stress were determined in vivo by magnetic resonance imaging and the gene expressions of ANF and SR Ca(2+)-ATPase were quantified by Northern blot. Low doses of both drugs did not affect blood pressure, hypertrophy, systolic wall stress and the ANF and SR Ca(2+)-ATPase gene expression. High doses of each drug reduced systolic blood pressure, wall stress, and LV hypertrophy to a similar extent and to values comparable to normotensive, age-matched rats. In addition, high dose treatment reduced LV end-systolic and end-diastolic volume as compared to untreated 2K-1C animals and normalized the mRNA levels of both ANF and SR Ca(2+)-ATPase (as compared to normotensive animals).. We conclude that in this model, high doses of ACE inhibition and AT1-receptor blockade are necessary to normalize systolic blood pressure, LV hypertrophy and systolic LV wall stress which, in turn, is associated with restoration of a normal cardiac phenotype with respect to SR Ca(2+)-ATPase and ANF and normalization of cardiac function.

Topics: Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Atrial Natriuretic Factor; Benzazepines; Blotting, Northern; Calcium-Transporting ATPases; Dose-Response Relationship, Drug; Heart Ventricles; Hypertension, Renal; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Rats; Rats, Inbred WKY; Sarcoplasmic Reticulum; Tetrazoles; Valine; Valsartan

The pharmacokinetics and pharmacodynamics of benazepril, an angiotensin converting enzyme (ACE) inhibitor, were investigated after administration of a single oral 5-mg dose and 7 more doses on consecutive days to hypertensive patients with normal renal function (NRF) and those with impaired renal function (IRF). The antihypertensive effect of benazepril was observed as early as 30 min after a single dose, and those effects during consecutive dosing were also sustained for 24 h with a lesser diurnal variation in blood pressure (BP). The time to peak (Tmax) and the apparent elimination half-life (t1/2) for benazepril were 0.6-0.7 h and 0.4-0.8 h, respectively. Tmax for its diacid was 1.5-2.4 h in both groups. The area under the plasma concentration-time curve to 24 h (AUC0-24h) for the diacid was significantly greater in the IRF group than in the NRF group. After consecutive dosing of benazepril, AUC0-24h and plasma peak level (Cmax) were significantly increased in the IRF group. Serum ACE activity was markedly suppressed for 24 h after administration, and the inhibition was closely related to plasma diacid levels. A significant inverse correlation was observed between creatinine clearance and the AUC for the diacid. These results suggest that benazepril is rapidly bioactivated to diacid and exhibits rapid onset and long-lasting antihypertensive effects. Dosage reduction might be required to minimize unnecessary drug accumulation in patients with severe IRF.

Topics: Administration, Oral; Angiotensin-Converting Enzyme Inhibitors; Benzazepines; Blood Pressure; Chromatography, High Pressure Liquid; Female; Half-Life; Humans; Hypertension, Renal; Kidney; Kidney Failure, Chronic; Male; Middle Aged; Peptidyl-Dipeptidase A; Radioimmunoassay

Male Munich-Wistar rats were subjected to 1 2/3 nephrectomy. One group received no therapy (C). A second group received daily doses of methylprednisolone (MP). A third group received MP plus the angiotensin I converting enzyme inhibitor (CEI) benzazepril. A fourth group received CEI alone. Half of the rats in each group underwent micropuncture study 2 weeks after ablation. Untreated rats exhibited systemic hypertension and elevation of the single nephron glomerular filtration rate (SNGFR), due to glomerular capillary hyperperfusion and hypertension. Administration of MP resulted in comparable systemic hypertension with further elevation of SNGFR due to even higher values for glomerular perfusion and hydraulic pressure (PGC). Concurrent treatment with CEI-controlled systemic and glomerular hypertension despite equivalent renal ablation and comparable doses of MP. After 12 weeks untreated rats demonstrated continued systemic hypertension, progressive proteinuria, and eventual glomerular sclerosis. Addition of MP dramatically accelerated the development of proteinuria and glomerular sclerosis, while CEI afforded striking protection against disease progression. Thus, potent vasodilator glucocorticoids may amplify hemodynamically mediated glomerular injury, whereas control of systemic and glomerular hypertension prevents this undesirable consequence of chronic steroid therapy.

Topics: Analysis of Variance; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Disease Models, Animal; Glomerular Filtration Rate; Glucocorticoids; Hypertension, Renal; Kidney Glomerulus; Male; Methylprednisolone; Nephrectomy; Nephrons; Proteinuria; Rats; Rats, Inbred Strains; Renal Circulation